Author: "Luc Dupuis" / Publisher: hal ccsd - Searchworks@Jio Institute Digital Library Search Results

28 results on '"Luc Dupuis"'

1. Atxn2-CAG100-KnockIn mouse spinal cord shows progressive TDP43 pathology associated with cholesterol biosynthesis suppression

Author: Nesli-Ece Sen, Claudia Doering, Stéphane Dieterlé, R. Koenig, Suzana Gispert-Sanchez, Júlia Canet-Pons, Frédérique René, N. Hein-Fuchs, Anja Kerksiek, Melanie Vanessa Halbach, Aleksandar Arsovic, Gina Picchiarelli, D. Luetjohann, Jana Key, L.-E. Almaguer-Mederos, Raphaelle Cassel, Luc Dupuis, Georg Auburger, Goethe-Universität Frankfurt am Main, University Hospital Bonn, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Paul-Ehrlich-Institute - Federal Institute for Vaccines and Biomedicines (EPI), and Dieterle, Stéphane
Subjects: 0301 basic medicine, TIA1, [SDV]Life Sciences [q-bio], Tauopathy, Olivo-ponto-cerebellar atrophy, Demyelination, Steroidogenesis, Leukoencephalopathy, Neuroanatomie, Neuroinfammation, Biology, Neuroprotection, lcsh:RC321-571, Mice, 03 medical and health sciences, 0302 clinical medicine, Stress granule, Downregulation and upregulation, Neuroinflammation, medicine, Animals, Spinocerebellar Ataxias, Gene Knock-In Techniques, Amyotrophic lateral sclerosis, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Ataxin-2, 030304 developmental biology, Denervation, 0303 health sciences, medicine.disease, Astrogliosis, Cell biology, [SDV] Life Sciences [q-bio], Disease Models, Animal, Cholesterol, 030104 developmental biology, Spinal Cord, Neurology, TDP-43 Proteinopathies, Spinocerebellar ataxia, 030217 neurology & neurosurgery
Abstract: Large polyglutamine expansions in Ataxin-2 (ATXN2) cause multi-system nervous atrophy in Spinocerebellar Ataxia type 2 (SCA2). Intermediate size expansions carry a risk for selective motor neuron degeneration, known as Amyotrophic Lateral Sclerosis (ALS). Conversely, the depletion of ATXN2 prevents disease progression in ALS. Although ATXN2 interacts directly with RNA, and in ALS pathogenesis there is a crucial role of RNA toxicity, the affected functional pathways remain ill defined. Here, we examined an authentic SCA2 mouse model withAtxn2-CAG100-KnockIn for a first definition of molecular mechanisms in spinal cord pathology. Neurophysiology of lower limbs detected sensory neuropathy rather than motor denervation. Triple immunofluorescence demonstrated cytosolic ATXN2 aggregates sequestrating TDP43 and TIA1 from the nucleus. In immunoblots, this was accompanied by elevated CASP3, RIPK1 and PQBP1 abundance. RT-qPCR showed increase ofGrn,Tlr7andRnaset2mRNA versusEif5a2,Dcp2, Uhmk1andKif5adecrease. These SCA2 findings overlap well with known ALS features. Similar to other ataxias and dystonias, decreased mRNA levels forUnc80,Tacr1,Gnal,Ano3,Kcna2,Elovl5andCdr1contrasted withGpnmbincrease. Preterminal stage tissue showed strongly activated microglia containing ATXN2 aggregates, with parallel astrogliosis. Global transcriptome profiles from stages of incipient motor deficit versus preterminal age identified molecules with progressive downregulation, where a cluster of cholesterol biosynthesis enzymes includingDhcr24,Msmo1,Idi1andHmgcs1was prominent. Gas chromatography demonstrated a massive loss of crucial cholesterol precursor metabolites. Overall, the ATXN2 protein aggregation process affects diverse subcellular compartments, in particular stress granules, endoplasmic reticulum and receptor tyrosine kinase signaling. These findings identify new targets and potential biomarkers for neuroprotective therapies.
Published: 2021

2. Dysregulation of energy homeostasis in amyotrophic lateral sclerosis

Author: Luc Dupuis, Simon J Guillot, Matei Bolborea, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Warwick [Coventry], and Dieterle, Stéphane
Subjects: [SDV]Life Sciences [q-bio], Population, Disease, Carbohydrate metabolism, Bioinformatics, Energy homeostasis, 03 medical and health sciences, 0302 clinical medicine, Weight loss, medicine, Homeostasis, Humans, Amyotrophic lateral sclerosis, education, 030304 developmental biology, Motor Neurons, 0303 health sciences, education.field_of_study, business.industry, Amyotrophic Lateral Sclerosis, Neurodegenerative Diseases, medicine.disease, 3. Good health, Clinical trial, [SDV] Life Sciences [q-bio], Metabolic pathway, Neurology, Neurology (clinical), medicine.symptom, business, Energy Metabolism, 030217 neurology & neurosurgery
Abstract: Purpose of review Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease targeting upper and lower motor neurons, inexorably leading to an early death. Defects in energy metabolism have been associated with ALS, including weight loss, increased energy expenditure, decreased body fat mass and increased use of lipid nutrients at the expense of carbohydrates. We review here recent findings on impaired energy metabolism in ALS, and its clinical importance. Recent findings Hypothalamic atrophy, as well as alterations in hypothalamic peptides controlling energy metabolism, have been associated with metabolic derangements. Recent studies showed that mutations causing familial ALS impact various metabolic pathways, in particular mitochondrial function, and lipid and carbohydrate metabolism, which could underlie these metabolic defects in patients. Importantly, slowing weight loss, through high caloric diets, is a promising therapeutic strategy, and early clinical trials indicated that it might improve survival in at least a subset of patients. More research is needed to improve these therapeutic strategies, define pharmacological options, and refine the population of ALS patients that would benefit from these approaches. Summary Dysfunctional energy homeostasis is a major feature of ALS clinical picture and emerges as a potential therapeutic target.
Published: 2021

3. Linking neuroinflammation to motor neuron degeneration in ALS: The critical role of CXCL13/CXCR5

Author: Alizée Arnoux, Luc Dupuis, Laboratoire de pharmacologie et de toxicologie neurocardiovasculaire (LPTNC), Université de Strasbourg (UNISTRA), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dieterle, Stéphane
Subjects: Receptors, CXCR5, metabolism, pathology, [SDV]Life Sciences [q-bio], Aucun, MESH: Disease Susceptibility, lcsh:Medicine, MESH: Receptors, CXCR5, General Biochemistry, Genetics and Molecular Biology, CXCR5, MESH: Nerve Degeneration, 03 medical and health sciences, 0302 clinical medicine, Humans, Medicine, 030212 general & internal medicine, CXCL13, etiology, Neuroinflammation, ComputingMilieux_MISCELLANEOUS, MESH: Amyotrophic Lateral Sclerosis, Motor Neurons, lcsh:R5-920, MESH: Humans, business.industry, Amyotrophic Lateral Sclerosis, lcsh:R, General Medicine, genetics, Chemokine CXCL13, [SDV] Life Sciences [q-bio], Nerve Degeneration, Commentary, Motor neuron degeneration, Disease Susceptibility, MESH: Chemokine CXCL13, lcsh:Medicine (General), business, Neuroscience, 030217 neurology & neurosurgery, MESH: Motor Neurons
Abstract: International audience; No abstract available
Published: 2021

4. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis

Author: Torsten Grehl, Bertold Schrank, Johannes Dorst, Matthias Boentert, Jens Dreyhaupt, Daniel Zeller, Susanne Petri, Markus Otto, Franceso Roselli, Julian Grosskreutz, Thomas Meyer, Joachim Schuster, Andreas Hermann, Luc Dupuis, Simon Witzel, Andrea Sylvia Winkler, Johannes Prudlo, Stanislav Gorbulev, Ulrike Weiland, Jochen H. Weishaupt, Berit Jordan, Albert C. Ludolph, Jan Kassubek, University of Ulm (UUlm), Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ruhr-Universität Bochum [Bochum], Technische Universität Dresden = Dresden University of Technology (TU Dresden), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University of Rostock, Martin-Luther-University Halle-Wittenberg, Heidelberg University Hospital [Heidelberg], Jena University Hospital [Jena], University of Würzburg = Universität Würzburg, University of Münster, DKD Helios Klinik Wiesbaden [Wiesbaden, Germany] (DKD HELIOS Medical Center), University Medical Center Rostock, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University Medical Center [Mainz], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Technical University of Munich (TUM), Westfälische Wilhelms-Universität Münster = University of Münster (WWU), and Dieterle, Stéphane
Subjects: Male, medicine.medical_specialty, Neurofilament, [SDV]Life Sciences [q-bio], blood [Neurofilament Proteins], Placebo, Diet, High-Fat, Gastroenterology, 03 medical and health sciences, blood [Amyotrophic Lateral Sclerosis], 0302 clinical medicine, Neurofilament Proteins, Internal medicine, Post-hoc analysis, medicine, Humans, ddc:610, Amyotrophic lateral sclerosis, MESH: Neurofilament Proteins, ComputingMilieux_MISCELLANEOUS, MESH: Amyotrophic Lateral Sclerosis, Randomized Controlled Trials as Topic, MESH: Humans, MESH: Middle Aged, business.industry, Therapeutic effect, Amyotrophic Lateral Sclerosis, Middle Aged, medicine.disease, MESH: Male, 3. Good health, Riluzole, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, MESH: Diet, High-Fat, MESH: Randomized Controlled Trials as Topic, Tolerability, statistics & numerical data [Randomized Controlled Trials as Topic], motor neuron disease, Population study, Surgery, Female, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery, medicine.drug
Abstract: Recent publications showed that circulating neurofilaments (Nfs) may be used as a diagnostic biomarker distinguishing amyotrophic lateral sclerosis (ALS) from ALS mimics with high sensitivity and specificity.1–3 Furthermore, it has been shown that patients with higher Nf levels show faster disease progression1 and shorter survival.2 3 Nf levels remain rather stable during the course of disease.2 Current literature suggests that the diagnostic value of neurofilament light chains (NfL) and phosphorylated neurofilament heavy chains in cerebrospinal fluid is about equal, whereas in blood NfL seems to be superior.4 In this study, we investigated the effect of a high-caloric fatty diet (HCFD) on NfL serum levels, using blood samples collected during the LIPCAL-ALS (efficacy, safety and tolerability of high lipid and caloriesupplementation in amyotrophic lateral sclerosis) study, a randomised, double-blind, parallel-group, placebo-controlled, multicentre trial, which investigated the therapeutic effect of HCFD in ALS.5 In LIPCAL-ALS, 201 patients (80 women, 121 men, age 62.4±10.8) were randomly assigned (1:1) to receive either HCFD (405 kcal/day, 100% fat) or placebo in addition to riluzole (100 mg/day) for 18 months. Although the primary outcome overall survival was negative in the whole study population (p=0.44), the post hoc analysis revealed a significantly longer survival for fast-progressing patients (ie, patients with an Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) slope >median between disease onset and baseline) in the HCFD group compared with placebo.5 To further corroborate our hypothesis of a disease-modifying effect of HCFD, we analysed NfL serum levels from LIPCAL-ALS participants. At each on-site visit during LIPCAL-ALS (6-month intervals), patients were asked if they were willing to provide an additional serum sample for NfL analysis on a voluntary basis. Serum NfL concentrations were measured with the single molecule array (Simoa) platform provided by Quanterix (Lexington, Massachusetts, USA) with single measurements …
Published: 2020

5. Association of Insulin-like Growth Factor 1 Concentrations with Risk for and Prognosis of Amyotrophic Lateral Sclerosis - Results from the ALS Registry Swabia

Author: Dietrich Rothenbacher, Angela Rosenbohm, Wolfgang Koenig, Albert C. Ludolph, Gabriele Nagel, Raphael Simon Peter, Luc Dupuis, Institute of Epidemiology and Medical Biometry [Ulm, Allemagne], Universität Ulm - Ulm University [Ulm, Allemagne], Department of Neurology [Ulm, Allemagne], Deutsches Herzzentrum München [Munich, Allemagne] (DHM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Munich Heart Alliance [Munich, Allemagne] (MHA), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), The ALS registry Swabia and this study have been supported by the German Research Council (DFG)., and Bodescot, Myriam
Subjects: Male, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, lcsh:Medicine, Cohort Studies, Prognostic markers, Insulin-like growth factor, 0302 clinical medicine, Germany, Registries, Insulin-Like Growth Factor I, Amyotrophic lateral sclerosis, lcsh:Science, 0303 health sciences, Multidisciplinary, Middle Aged, Prognosis, Survival Rate, Quartile, Female, Cohort study, Risk, medicine.medical_specialty, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Survival rate, Aged, Proportional Hazards Models, 030304 developmental biology, business.industry, Proportional hazards model, Amyotrophic Lateral Sclerosis, lcsh:R, Case-control study, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Serum samples, Logistic Models, Risk factors, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: We investigated the associations of serum concentration of insulin-like growth factor 1 (IGF1) with risk and prognosis of ALS in the ALS registry (October 2010–June 2014, median follow-up 67.6 months) in a case-control and cohort study, respectively. Serum samples were measured for IGF-1. Information on covariates was collected by standardized questionnaire. We applied conditional logistic regression to appraise the risk and Cox proportional hazards models to appraise the prognostic value of IGF-1. Data of 294 ALS patients (mean age 65.4 (SD 11.0) years, 60.2% men) and 504 controls were included in the case-control study. Median serum IGF-1 concentrations were slightly higher in ALS cases than in controls (101 vs. 99.5 ng/ml). IGF-1 concentrations were not associated with ALS risk in the fully adjusted model (top vs. bottom quartile: OR 1.16; 95%-CI 0.73–1.84, p for trend = 0.44). Among 293 ALS cases (mean age 65.5 (SD 10.5) years, 56.8% men) 243 died during follow-up. We found a statistically significant inverse association between continuous IGF-1 concentrations and survival (p = 0.01). Very high values IGF-1 were associated with a better prognosis of ALS suggesting that functions related to IGF-1 could be involved in survival.
Published: 2020

6. Effect of High‐Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis

Author: Johannes Prudlo, Ulrike Weiland, Susanne Petri, Jens Dreyhaupt, Thomas F. Meyer, Bertold Schrank, Albert C. Ludolph, Daniel Zeller, Julian Grosskreutz, Luc Dupuis, Andrea Sylvia Winkler, Francesco Roselli, Andreas Hermann, Jochen H. Weishaupt, Jan Kassubek, Johannes Dorst, Alexander Emmer, Matthias Boentert, Torsten Grehl, Joachim Schuster, Stanislav Gorbulev, University of Ulm (UUlm), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Humboldt University of Berlin, Hannover Medical School [Hannover] (MHH), Technische Universität Dresden = Dresden University of Technology (TU Dresden), University of Rostock, Martin-Luther-University Halle-Wittenberg, Jena University Hospital [Jena], Ruhr-Universität Bochum [Bochum], University of Würzburg = Universität Würzburg, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), DKD Helios Klinik Wiesbaden [Wiesbaden, Germany] (DKD HELIOS Medical Center), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), University Medical Center [Mainz], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), LIPCAL-ALS Study Group., Technical University of Munich (TUM), Dieterle, Stéphane, and Humboldt University Of Berlin
Subjects: Male, 0301 basic medicine, mortality [Amyotrophic Lateral Sclerosis], MESH: Combined Modality Therapy, [SDV]Life Sciences [q-bio], law.invention, 0302 clinical medicine, MESH: Riluzole, Randomized controlled trial, law, diet therapy [Amyotrophic Lateral Sclerosis], Clinical endpoint, Medicine, MESH: Double-Blind Method, therapeutic use [Riluzole], MESH: Amyotrophic Lateral Sclerosis, methods [Combined Modality Therapy], education.field_of_study, Riluzole, MESH: Middle Aged, Hazard ratio, MESH: Neuroprotective Agents, Middle Aged, therapeutic use [Neuroprotective Agents], Combined Modality Therapy, 3. Good health, [SDV] Life Sciences [q-bio], Neuroprotective Agents, Neurology, MESH: Survival Analysis, Female, medicine.drug, mortality [Diet, High-Fat], medicine.medical_specialty, Population, Diet, High-Fat, Placebo, 03 medical and health sciences, Double-Blind Method, Internal medicine, Humans, ddc:610, education, Survival analysis, MESH: Humans, drug therapy [Amyotrophic Lateral Sclerosis], business.industry, Amyotrophic Lateral Sclerosis, Survival Analysis, Confidence interval, MESH: Male, MESH: Diet, High-Fat, 030104 developmental biology, Neurology (clinical), business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Objective: Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival.Methods: A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018. Patients were followed up at 3, 6, 9, 12, 15, and 18 months after randomization. The study was performed at 12 sites of the clinical and scientific network of German motor neuron disease centers (ALS/MND-NET). Eligible patients were randomly assigned (1:1) to receive either HCFD (405kcal/day, 100% fat) or placebo in addition to riluzole (100mg/day). The primary endpoint was survival time, defined as time to death or time to study cutoff date.Results: Two hundred one patients (80 female, 121 male, age = 62.4 ± 10.8 years) were included. The confirmatory analysis of the primary outcome survival showed a survival probability of 0.39 (95% confidence interval [CI] = 0.27-0.51) in the placebo group and 0.37 (95% CI = 0.25-0.49) in the HCFD group, both after 28 months (point in time of the last event). The hazard ratio was 0.97, 1-sided 97.5% CI = -∞ to 1.44, p = 0.44.Interpretation: The results provide no evidence for a life-prolonging effect of HCFD for the whole amyotrophic lateral sclerosis population. However, post hoc analysis revealed a significant survival benefit for the subgroup of fast-progressing patients. ANN NEUROL 2020;87:206-216.
Published: 2019

7. FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis

Author: Chantal Sellier, Nick H.M. van Bakel, Amila Zuko, Céline Sijlmans, Sina Mersmann, Anne-Laurence Boutillier, Annemarie Hübers, Amr Aly, Marina Wagner, Stéphane Dieterlé, Moushami Mallik, Marc-Antoine Goy, Clotilde Lagier-Tourenne, Gina Picchiarelli, Albert C. Ludolph, Luc Dupuis, Erik Storkebaum, Julia Higelin, Angela Rosenbohm, Li Zhang, Tobias M. Boeckers, Marije Been, Maria Demestre, Jelena Scekic-Zahirovic, Nadia Messaddeq, Inmaculada Sanjuan-Ruiz, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie, Universität Ulm - Ulm University [Ulm, Allemagne], Institut for Anatomy and Cell Biology, Laboratoire de neurosciences cognitives et adaptatives (LNCA), and Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Muscle Fibers, Skeletal, metabolism [Neuromuscular Junction], Mice, 0302 clinical medicine, Postsynaptic potential, Receptors, Cholinergic, Gene Knock-In Techniques, Amyotrophic lateral sclerosis, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Molecular Neurobiology, metabolism [RNA-Binding Protein FUS], Mice, Knockout, Motor Neurons, physiology [RNA-Binding Protein FUS], Myogenesis, General Neuroscience, ETS transcription factor family, FUS protein, mouse, physiopathology [Amyotrophic Lateral Sclerosis], medicine.anatomical_structure, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Adult, pathology [Motor Neurons], physiology [Gene Expression Regulation], Neuromuscular Junction, Biology, pathology [Neuromuscular Junction], Neuromuscular junction, Article, 03 medical and health sciences, Young Adult, ddc:570, metabolism [Receptors, Cholinergic], medicine, Animals, Humans, pathology [Amyotrophic Lateral Sclerosis], Acetylcholine receptor, [SCCO.NEUR]Cognitive science/Neuroscience, Amyotrophic Lateral Sclerosis, Skeletal muscle, Motor neuron, physiopathology [Nerve Degeneration], medicine.disease, 030104 developmental biology, Gene Expression Regulation, Nerve Degeneration, RNA-Binding Protein FUS, pathology [Muscle Fibers, Skeletal], genetics [RNA-Binding Protein FUS], Neuroscience, 030217 neurology & neurosurgery
Abstract: Neuromuscular junction (NMJ) disruption is an early pathogenic event in amyotrophic lateral sclerosis (ALS). Yet, direct links between NMJ pathways and ALS-associated genes such as FUS, whose heterozygous mutations cause aggressive forms of ALS, remain elusive. In a knock-in Fus-ALS mouse model, we identified postsynaptic NMJ defects in newborn homozygous mutants that were attributable to mutant FUS toxicity in skeletal muscle. Adult heterozygous knock-in mice displayed smaller neuromuscular endplates that denervated before motor neuron loss, which is consistent with 'dying-back' neuronopathy. FUS was enriched in subsynaptic myonuclei, and this innervation-dependent enrichment was distorted in FUS-ALS. Mechanistically, FUS collaborates with the ETS transcription factor ERM to stimulate transcription of acetylcholine receptor genes. Co-cultures of induced pluripotent stem cell-derived motor neurons and myotubes from patients with FUS-ALS revealed endplate maturation defects due to intrinsic FUS toxicity in both motor neurons and myotubes. Thus, FUS regulates acetylcholine receptor gene expression in subsynaptic myonuclei, and muscle-intrinsic toxicity of ALS mutant FUS may contribute to dying-back motor neuronopathy.
Published: 2019

8. Paradox of amyotrophic lateral sclerosis and energy metabolism

Author: Luc Dupuis, Matthew C. Kiernan, Rebekah M. Ahmed, Royal Prince Alfred Hospital [Sydney, Australia], The University of Sydney, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dieterle, Stéphane
Subjects: Weakness, medicine.medical_specialty, [SDV]Life Sciences [q-bio], MESH: Frontotemporal Dementia, Disease, frontotemporal dementia, Fasciculation, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Resting energy expenditure, 030212 general & internal medicine, Amyotrophic lateral sclerosis, ComputingMilieux_MISCELLANEOUS, MESH: Amyotrophic Lateral Sclerosis, Denervation, MESH: Humans, business.industry, MESH: Energy Metabolism, medicine.disease, Muscle atrophy, 3. Good health, [SDV] Life Sciences [q-bio], Psychiatry and Mental health, Cardiology, motor neuron disease, Surgery, Neurology (clinical), MESH: C9orf72 Protein, medicine.symptom, business, 030217 neurology & neurosurgery, Frontotemporal dementia
Abstract: Amyotrophic lateral sclerosis (ALS) is a disease of paradoxes. Patients usually have little or no medical history and tend to be fit and athletic,1 2 yet undergo a rapid, unrelenting decline. Patients predominantly present with progressive weakness, with involvement of cortical motor neurons and as the disease progresses, patients develop denervation, muscle atrophy, decreased muscle mass and decreased free fat mass, all of which would be expected to decrease energy expenditure.3 Yet patients with ALS are consistently hypermetabolic, with increased resting energy expenditure evident in up to 50% of patients.4 Several variables have been hypothesised to contribute to this hypermetabolic state, including uncontrolled fasciculations, increased respiratory work and mitochondrial dysfunction,4 yet the exact mechanism remains to be elucidated. In their JNNP paper Steyn and colleagues5 aim to …
Published: 2018

9. The VAMP‐associated protein VAPB is required for cardiac and neuronal pacemaker channel function

Author: Nicole, Silbernagel, Magdalena, Walecki, Martin K-H, Schäfer, Mirjam, Kessler, Mehrnoush, Zobeiri, Susanne, Rinné, Aytug K, Kiper, Marlene A, Komadowski, Kirsty S, Vowinkel, Konstantin, Wemhöner, Lisa, Fortmüller, Marcus, Schewe, Amalia M, Dolga, Jelena, Scekic-Zahirovic, Lina A, Matschke, Carsten, Culmsee, Thomas, Baukrowitz, Laurent, Monassier, Nina D, Ullrich, Luc, Dupuis, Steffen, Just, Thomas, Budde, Larissa, Fabritz, Niels, Decher, Phillips University [Marburg, Germany] (PU), Universitätsklinikum Ulm - University Hospital of Ulm, University of Münster, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Christian-Albrechts University of Kiel, Laboratoire de pharmacologie et de toxicologie neurocardiovasculaire (LPTNC), Université de Strasbourg (UNISTRA), Universität Heidelberg [Heidelberg], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospitals Birmingham [Birmingham, Royaume-Uni], University of Birmingham [Birmingham], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), and Dieterle, Stéphane
Subjects: Pacemaker, Artificial, Embryo, Nonmammalian, MESH: Vesicular Transport Proteins, MESH: Rats, [SDV]Life Sciences [q-bio], Vesicular Transport Proteins, MESH: Neurons, MESH: Carrier Proteins, MESH: Rats, Sprague-Dawley, MESH: Mice, Knockout, Rats, Sprague-Dawley, HCN channels, Mice, Xenopus laevis, cardiac arrhythmia, MESH: Xenopus laevis, Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, Animals, Humans, MESH: Animals, MESH: Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels, MESH: Zebrafish, MESH: Mice, Zebrafish, Mice, Knockout, Neurons, MESH: Humans, Research, Membrane Proteins, MESH: Embryo, Nonmammalian, Heart, MESH: Ion Channel Gating, Rats, [SDV] Life Sciences [q-bio], MESH: Heart, MESH: HeLa Cells, MESH: Pacemaker, Artificial, Female, MESH: Membrane Proteins, ALS, Carrier Proteins, Ion Channel Gating, MESH: Female, HeLa Cells
Abstract: International audience; Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels encode neuronal and cardiac pacemaker currents. The composition of pacemaker channel complexes in different tissues is poorly understood, and the presence of additional HCN modulating subunits was speculated. Here we show that vesicle-associated membrane protein-associated protein B (VAPB), previously associated with a familial form of amyotrophic lateral sclerosis 8, is an essential HCN1 and HCN2 modulator. VAPB significantly increases HCN2 currents and surface expression and has a major influence on the dendritic neuronal distribution of HCN2. Severe cardiac bradycardias in VAPB-deficient zebrafish and VAPB-/- mice highlight that VAPB physiologically serves to increase cardiac pacemaker currents. An altered T-wave morphology observed in the ECGs of VAPB-/- mice supports the recently proposed role of HCN channels for ventricular repolarization. The critical function of VAPB in native pacemaker channel complexes will be relevant for our understanding of cardiac arrhythmias and epilepsies, and provides an unexpected link between these diseases and amyotrophic lateral sclerosis.-Silbernagel, N., Walecki, M., Schäfer, M.-K. H., Kessler, M., Zobeiri, M., Rinné, S., Kiper, A. K., Komadowski, M. A., Vowinkel, K. S., Wemhöner, K., Fortmüller, L., Schewe, M., Dolga, A. M., Scekic-Zahirovic, J., Matschke, L. A., Culmsee, C., Baukrowitz, T., Monassier, L., Ullrich, N. D., Dupuis, L., Just, S., Budde, T., Fabritz, L., Decher, N. The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function.
Published: 2018

10. Association of Serum Retinol-Binding Protein 4 Concentration With Risk for and Prognosis of Amyotrophic Lateral Sclerosis

Author: Dietrich Rothenbacher, Raphael Simon Peter, Luc Dupuis, Albert C. Ludolph, Gabriele Nagel, Torben Brehme, Angela Rosenbohm, Wolfgang Koenig, University of Ulm (UUlm), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), ALS Registry Study Group: B Alber, F Andres, G Arnold, I Asshauer, H Baezner, H Baier, J Beattie, T Becker, F Behne, D Bengel, A Boertlein, V Bracknies, R Broer, B Connemann, S Dempewolf, C Dettmers, M Dieterich, E Etzersdorfer, W Freund, T Gersner, H Gold, W Hacke, G Hamann, M Hecht, B Heimbach, B Hemmer, C Hendrich, B Herting, R Huber, K Huber-Hartmann, P Hülser, E Jüttler, J Kammerer-Ciernioch, A Kaspar, R Kern, H Kimmig, S Klebe, C Kloetzsch, T Klopstock, A Kohler, A Kuethmann, D Lewis, C Lichy, A Lindner, D Lulé, M Mäurer, W Maier-Janson, J Metrikat, O Meudt, A Meyer, J Müller vom Hagen, A Naegele, M Naumann, K Neher, O Neuhaus, C Neusch, C Opherk, J Raape, P Ratzka, C Rettenmayr, M Riepe, J Rothmeier, M Sabolek, M Schabet, C Schell, T Schlipf, M Schmauss, L Schoels, K Schuetz, B Schweigert, N Sommer, W Sperber, C Steber, R Steber, M Stroick, M Synofzik, T Trottenberg, H Tumani, C Wahl, F Weber, M Weiler, C Weiller, C Wessig, A Winkler., Dieterle, Stéphane, Klebe, Stephan (Beitragende*r), and Technische Universität München [München] (TUM)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], Medizin, MESH: Community Health Planning, MESH: Logistic Models, Cohort Studies, Fats, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Germany, Amyotrophic lateral sclerosis, Vitamin A, MESH: Cohort Studies, MESH: Amyotrophic Lateral Sclerosis, MESH: Vitamin A, Original Investigation, 2. Zero hunger, MESH: Aged, education.field_of_study, MESH: Middle Aged, Middle Aged, Prognosis, MESH: Case-Control Studies, 3. Good health, [SDV] Life Sciences [q-bio], Quartile, Female, MESH: Retinol-Binding Proteins, Plasma, Cohort study, medicine.medical_specialty, Population, Community Health Planning, MESH: Prognosis, 03 medical and health sciences, Insulin resistance, MESH: Fats, Internal medicine, medicine, Humans, education, MESH: Germany, Survival analysis, Aged, MESH: Humans, business.industry, Amyotrophic Lateral Sclerosis, Case-control study, Odds ratio, medicine.disease, MESH: Male, Logistic Models, 030104 developmental biology, Case-Control Studies, Neurology (clinical), business, Retinol-Binding Proteins, Plasma, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Importance: Knowledge about the metabolic states of patients with amyotrophic lateral sclerosis (ALS) may provide a therapeutic approach.Objective: To investigate the association between the onset and prognosis of ALS and serum retinol-binding protein 4 (RBP4) concentration as a biomarker for insulin resistance and vitamin A metabolism.Design, setting, and participants: Case-control design for risk factors of ALS; cohort design for prognostic factors within ALS cases. Between October 1, 2010, and June 30, 2014, a population-based case-control study with randomly selected controls was established based on the ALS Registry Swabia in southern Germany, with a target population of 8.4 million inhabitants. Response rates were 64.8% among the cases and 18.7% among the controls. The dates of analysis were April 2016 to May 2017.Main outcomes and measures: Serum samples were measured for RBP4. Information on covariates was assessed by an interview-based standardized questionnaire. Main outcomes and measures were adjusted odds ratios for risk of ALS associated with serum RBP4 concentration, as well as time to death associated with RBP4 concentration at baseline in ALS cases only. Conditional logistic regression was applied to calculate multivariable odds ratios for risk of ALS. Survival models were used in cases only to appraise their prognostic value.Results: Data from 289 patients with ALS (mean [SD] age, 65.7 [10.5] years; 172 [59.5%] male) and 504 controls (mean [SD] age, 66.3 [9.8] years; 299 [59.3%] male) were included in the case-control study. Compared with controls, ALS cases were characterized by lower body mass index, less educational attainment, smoking, light occupational work intensity, and self-reported diabetes. The median serum RBP4 concentration was lower in ALS cases than in controls (54.0 vs 59.5 mg/L). In the multivariable model, increasing RBP4 concentration was associated with reduced odds for ALS (top vs bottom quartile odds ratio, 0.36; 95% CI, 0.22-0.59; P for trend
Published: 2018

11. Thermoregulation in amyotrophic lateral sclerosis

Author: Luc Dupuis, Patrick Weydt, Åsa Petersén, Dieterle, Stéphane, Université de Strasbourg (UNISTRA), Lund University [Lund], and University of Bonn
Subjects: 0301 basic medicine, medicine.medical_specialty, amyotrophic lateral sclerosis, Neurology, TDP-43, [SDV]Life Sciences [q-bio], SOD1, PGC-1α, Disease, frontotemporal dementia, Energy homeostasis, 03 medical and health sciences, 0302 clinical medicine, medicine, Dementia, Humans, Amyotrophic lateral sclerosis, skeletal muscle, energy homeostasis, MESH: Amyotrophic Lateral Sclerosis, sympathetic nervous system, dynein, MESH: Humans, business.industry, brown adipose tissue, Thermoregulation, medicine.disease, [SDV] Life Sciences [q-bio], MESH: Body Temperature Regulation, 030104 developmental biology, business, Neuroscience, body temperature, 030217 neurology & neurosurgery, Frontotemporal dementia, Body Temperature Regulation
Abstract: International audience; Amyotrophic lateral sclerosis (ALS) is the major adult-onset motor neuron disease, and is clinically, pathologically, and genetically associated with frontotemporal dementia, the second cause of dementia in the elderly. Here, we review the evidence linking thermoregulation and ALS. Indeed, while ALS is not classically associated with defective thermoregulatory function, its progression severely affects key brain regions controlling body temperature and impacts multiple sensors and effectors of this homeostatic function. Furthermore, animal models of ALS display disturbed thermoregulation as a consequence of disrupted energy homeostasis. All these lines of indirect evidence call for studies directly addressing the body temperature regulatory system, both as a potential biomarker and as a possible modifier of disease progression in ALS.
Published: 2018

12. Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function

Author: Dorothee Dormann, Stefan Reber, Luc Dupuis, Helena Ederle, Marian Hruska-Plochan, Eva-Maria Hock, Marc-David Ruepp, Florent Laferrière, Zuzanna Maniecka, Lucas Pelkmans, M K Sonu Sahadevan, Tammaryn Lashley, Lauren M. Gittings, Magdalini Polymenidou, Dieterle, Stéphane, Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Bern, Ludwig Maximilian University [Munich] (LMU), UCL, Institute of Neurology [London], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), UK Dementia Research Institute (UK DRI), University College of London [London] (UCL), Universität Bern [Bern], Ludwig-Maximilians-Universität München (LMU), Institute of Neurology [London], King‘s College London, Universität Bern [Bern] (UNIBE), Laferriere, Florent, University of Zurich, and Polymenidou, Magdalini
Subjects: 0301 basic medicine, Cytoplasm, MESH: Hippocampus, Cytoplasmic inclusion, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], MESH: Neurons, Chromosomal translocation, RNA-binding protein, RNA-binding proteins, Hippocampus, Mice, ALS, FTD, FUS, stress granules, nucleocytoplasmic shuttling, Transportin, protein aggregation, MESH: Animals, Amyotrophic lateral sclerosis, Cerebral Cortex, Neurons, Chemistry, MESH: RNA-Binding Protein FUS, Cell biology, [SDV] Life Sciences [q-bio], MESH: HEK293 Cells, Transportin 1, MESH: Cell Nucleus, 610 Medicine & health, Genetics and Molecular Biology, Karyopherins, Transfection, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Stress granule, 1300 General Biochemistry, Genetics and Molecular Biology, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, MESH: Mice, Cell Nucleus, MESH: Humans, MESH: Cytoplasm, MESH: Transfection, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, MESH: Karyopherins, MESH: Cerebral Cortex, Mice, Inbred C57BL, MESH: Astrocytes, HEK293 Cells, 030104 developmental biology, Hypertonic Stress, Astrocytes, General Biochemistry, RNA-Binding Protein FUS, 11493 Department of Quantitative Biomedicine
Abstract: The primarily nuclear RNA-binding protein FUS (fused in sarcoma) forms pathological cytoplasmic inclusions in a subset of early-onset amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients. In response to cellular stress, FUS is recruited to cytoplasmic stress granules, which are hypothesized to act as precursors of pathological inclusions. We monitored the stress-induced nucleocytoplasmic shuttling of endogenous FUS in an ex vivo mouse CNS model and human neural networks. We found that hyperosmolar, but not oxidative, stress induced robust cytoplasmic translocation of neuronal FUS, with transient nuclear clearance and loss of function. Surprisingly, this reaction is independent of stress granule formation and the molecular pathways activated by hyperosmolarity. Instead, it represents a mechanism mediated by cytoplasmic redistribution of Transportin 1/2 and is potentiated by transcriptional inhibition. Importantly, astrocytes, which remain unaffected in ALS/FTD-FUS, are spared from this stress reaction that may signify the initial event in the development of FUS pathology., Cell Reports, 24 (4), ISSN:2666-3864, ISSN:2211-1247
Published: 2018

13. Adipokines, C-reactive protein and Amyotrophic Lateral Sclerosis – results from a population- based ALS registry in Germany

Author: Gabriele, Nagel, Raphael S, Peter, Angela, Rosenbohm, Wolfgang, Koenig, Luc, Dupuis, Dietrich, Rothenbacher, Albert C, Ludolph, University of Ulm (UUlm), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dieterle, Stéphane, and Technische Universität München [München] (TUM)
Subjects: Male, MESH: Registries, Science, [SDV]Life Sciences [q-bio], education, MESH: Disease Susceptibility, Article, MESH: Population Surveillance, [SCCO]Cognitive science, MESH: Adipokines, Adipokines, Germany, MESH: C-Reactive Protein, Odds Ratio, Humans, Registries, MESH: Germany, MESH: Amyotrophic Lateral Sclerosis, Aged, MESH: Aged, MESH: Humans, MESH: Middle Aged, Amyotrophic Lateral Sclerosis, [SCCO] Cognitive science, MESH: Follow-Up Studies, Middle Aged, Survival Analysis, MESH: Male, MESH: Odds Ratio, [SDV] Life Sciences [q-bio], C-Reactive Protein, Population Surveillance, MESH: Survival Analysis, MESH: Biomarkers, Medicine, Female, Disease Susceptibility, MESH: Female, Biomarkers, Follow-Up Studies
Abstract: International audience; To investigate the associations of leptin, adiponectin and high-sensitive (hs) C-reactive protein (CRP) with risk and prognosis of amyotrophic lateral sclerosis (ALS). Data from a population-based case-control study in Southern Germany (10/2010-6/2014) of 289 ALS patients (mean age of 65.7 (SD 10.5) years, 59.5% men) and 506 controls were included. During median follow-up of 14.5 months of 279 ALS patients 104 (53.9% men, 68.9 (10.3) years) died. Serum samples were measured for leptin, adiponectin and hs-CRP. Conditional logistic regression was used to estimate ALS risk. Survival models were used to appraise the prognostic value. ALS patients were characterized by lower levels of school education, BMI and smoking prevalence. Adjusted for covariates, leptin was inversely associated with ALS risk (top vs. bottom quartile: OR 0.49; 95% CI 0.29-0.80), while for adiponectin a positive association was found (OR 2.89; 95% CI 1.78-4.68). Among ALS patients increasing leptin concentrations were associated with longer survival (p for trend 0.002), while for adiponectin no association was found (p for trend 0.55). For hs-CRP no association was found. Leptin and adiponectin, two key hormones regulating energy metabolism, were strongly and independently related with ALS risk. Leptin levels were further negatively related with overall survival of ALS patients.
Published: 2017

14. Life course body mass index and risk and prognosis of amyotrophic lateral sclerosis: results from the ALS registry Swabia

Author: Albert C. Ludolph, Luc Dupuis, Jan Kassubek, Dietrich Rothenbacher, Angela Rosenbohm, Gabriele Nagel, Raphael Simon Peter, Torben Brehme, University of Ulm (UUlm), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dieterle, Stéphane
Subjects: Male, 0301 basic medicine, Weight loss, MESH: Registries, Epidemiology, [SDV]Life Sciences [q-bio], [SCCO]Cognitive science, 0302 clinical medicine, Germany, Medicine, Longitudinal Studies, Prospective Studies, Registries, Amyotrophic lateral sclerosis, MESH: Longitudinal Studies, Body mass index, MESH: Amyotrophic Lateral Sclerosis, 2. Zero hunger, MESH: Aged, education.field_of_study, Prognostic factor, MESH: Middle Aged, Weight change, Middle Aged, Prognosis, MESH: Case-Control Studies, 3. Good health, [SDV] Life Sciences [q-bio], Female, medicine.symptom, Adult, medicine.medical_specialty, Hypermetabolism, Population, MESH: Prognosis, MESH: Body Mass Index, 03 medical and health sciences, MESH: Weight Loss, Internal medicine, Humans, Risk factor, education, MESH: Germany, Aged, MESH: Humans, business.industry, MESH: Adult, Odds ratio, [SCCO] Cognitive science, medicine.disease, Confidence interval, MESH: Male, MESH: Prospective Studies, Surgery, 030104 developmental biology, Case-Control Studies, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; Weight loss appears as a strong predictor of survival of patients with amyotrophic lateral sclerosis, yet no data are currently available to describe the life course history of pre-diagnostic body mass index (BMI) in these patients. 393 ALS cases (mean age: 65.8 years, 57.3% men) and 791 controls matched by age and sex from a population-based case-control study of the ALS Registry Swabia were analyzed. Differences of BMI change in cases and controls over time were modeled using a multilevel additive model. In addition, survival in ALS cases by BMI change was modeled using an accelerated failure time model adjusted for prognostic factors. In ALS cases, BMI was consistently higher than in controls in the 20-70 years before the interview. Conditional logistic regression revealed an odds ratio of 1.05 (95% confidence interval (CI) 1.00-1.11, p = 0.041) per 1 kg/m2 higher BMI 35-45 years before interview. However, a sharp decrease was evident in the BMI of ALS cases about 10 years before disease onset. Moreover, weight loss was strongly associated with shorter survival in ALS patients. Illustrating this, patients with stable weight showed a median survival time of 22.1 (95%-CI 19.2-25.0) months, as compared to 13.4 (95%-CI 10.5-16.3) months for patients with weight loss of 2.5 kg/m2 over the last 3 months before the interview. Thus, alterations in body weight are present in ALS patients already decades before clinical manifestation of ALS, while weight loss precedes motor symptoms of several years and is associated with poor prognosis.
Published: 2017

15. ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues

Author: Anke Witting, Eva Buck, Tanja Lucas, Jasmin Sprissler, Karin M Danzer, Karlheinz Holzmann, Kerstin Lang, Lara Barteczko, Tobias M. Boeckers, Patrick Weydt, Maria Demestre, Luc Dupuis, Hanna Bayer, Katrin S. Lindenberg, Noemi Pasquarelli, Julia Higelin, Albert C. Ludolph, University of Ulm (UUlm), Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Bonn, and Dieterle, Stéphane
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], MESH: Neurons, PGC-1α, MESH: Protein Isoforms, [SCCO]Cognitive science, Superoxide Dismutase-1, 0302 clinical medicine, Adipose Tissue, Brown, Neurotrophic factors, Protein Isoforms, MESH: Animals, Amyotrophic lateral sclerosis, Induced pluripotent stem cell, MESH: Amyotrophic Lateral Sclerosis, MESH: Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, MESH: Superoxide Dismutase-1, Neurons, MESH: Muscle, Skeletal, MESH: RNA-Binding Protein FUS, Neurodegeneration, Brain, SOD1, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, [SDV] Life Sciences [q-bio], Neurology, PPARGC1A, MESH: Mutation, MESH: Rats, MESH: Mice, Transgenic, Induced Pluripotent Stem Cells, Mice, Transgenic, MESH: Zebrafish Proteins, Biology, MESH: Induced Pluripotent Stem Cells, Neuroprotection, MESH: Adipose Tissue, Brown, Cell Line, lcsh:RC321-571, 03 medical and health sciences, MESH: Brain, Lou Gehrig disease, MESH: Mice, Inbred C57BL, Coactivator, medicine, Animals, Humans, RNA, Messenger, Muscle, Skeletal, MESH: Zebrafish, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, FUS, MESH: RNA, Messenger, MESH: Humans, [SCCO] Cognitive science, medicine.disease, Rats, MESH: Cell Line, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Mutation, Cancer research, RNA-Binding Protein FUS, Lactate, MESH: Disease Models, Animal, 030217 neurology & neurosurgery
Abstract: International audience; Background: Monogenetic forms of amyotrophic lateral sclerosis (ALS) offer an opportunity for unraveling the molecular mechanisms underlying this devastating neurodegenerative disorder. In order to identify a link between ALS-related metabolic changes and neurodegeneration, we investigated whether ALS-causing mutations interfere with the peripheral and brain-specific expression and signaling of the metabolic master regulator PGC (PPAR gamma coactivator)-1α (PGC-1α).Methods: We analyzed the expression of PGC-1α isoforms and target genes in two mouse models of familial ALS and validated the stimulated PGC-1α signaling in primary adipocytes and neurons of these animal models and in iPS derived motoneurons of two ALS patients harboring two different frame-shift FUS/TLS mutations.Results: Mutations in SOD1 and FUS/TLS decrease Ppargc1a levels in the CNS whereas in muscle and brown adipose tissue Ppargc1a mRNA levels were increased. Probing the underlying mechanism in neurons, we identified the monocarboxylate lactate as a previously unrecognized potent and selective inducer of the CNS-specific PGC-1α isoforms. Lactate also induced genes like brain-derived neurotrophic factor, transcription factor EB and superoxide dismutase 3 that are down-regulated in PGC-1α deficient neurons. The lactate-induced CNS-specific PGC-1α signaling system is completely silenced in motoneurons derived from induced pluripotent stem cells obtained from two ALS patients harboring two different frame-shift FUS/TLS mutations.Conclusion: ALS mutations increase the canonical PGC-1α system in the periphery while inhibiting the CNS-specific isoforms. We identify lactate as an inducer of the neuronal PGC-1α system directly linking brain metabolism and neuroprotection. Changes in the PGC-1α system might be involved in the ALS accompanied metabolic changes and in neurodegeneration.
Published: 2017

16. Body fat distribution in Parkinson's disease: An MRI-based body fat quantification study

Author: Jan Kassubek, Albert C. Ludolph, Hans-Peter Müller, Denise Bernhardt, Luc Dupuis, University of Ulm (UUlm), Heidelberg Institute of Radiation Oncology [Heidelberg, Germany] (HIRO), Heidelberg University Hospital [Heidelberg], Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dieterle, Stéphane
Subjects: Leptin, Male, Parkinson's disease, [SDV]Life Sciences [q-bio], Statistics as Topic, Adipose tissue, Gastroenterology, Weight loss, Body Mass Index, MESH: Magnetic Resonance Imaging, [SCCO]Cognitive science, 0302 clinical medicine, MESH: Sequestosome-1 Protein, Image Processing, Computer-Assisted, Medicine, Mass index, 030212 general & internal medicine, MESH: Statistics, Nonparametric, medicine.diagnostic_test, MESH: Peptides, Parkinson Disease, MESH: Follow-Up Studies, MESH: Case-Control Studies, MESH: Image Processing, Computer-Assisted, [SDV] Life Sciences [q-bio], Adipose Tissue, Neurology, Female, medicine.symptom, MESH: Adipose Tissue, medicine.medical_specialty, Body fat distribution, MESH: Zebrafish Proteins, Statistics, Nonparametric, MESH: Protein-Serine-Threonine Kinases, MESH: Body Mass Index, 03 medical and health sciences, Magnetic resonance imaging, Internal medicine, Humans, MESH: Body Fat Distribution, MESH: Zebrafish, MESH: Statistics as Topic, MESH: Humans, MESH: Phosphorylation, business.industry, Body Weight, Case-control study, [SCCO] Cognitive science, MESH: Leptin, medicine.disease, MESH: Male, MESH: Body Weight, Endocrinology, Metabolism, Case-Control Studies, Neurology (clinical), Geriatrics and Gerontology, business, Body mass index, MESH: Female, 030217 neurology & neurosurgery, MESH: Parkinson Disease, Follow-Up Studies
Abstract: International audience; Introduction: There is some evidence that Parkinson's Disease (PD) patients have lower body weight and lower fat mass when compared to healthy subjects and that lower body weight and fat mass influence disease risk and progression. It remains unclear, however, if weight loss of fat mass loss occurs only in a subgroup of patients and whether fat distribution is altered during PD. The aim of this study was to prospectively investigate adipose tissue content and distribution in PD patients.Methods: The body fat composition of PD patients (N = 54) was compared with age matched healthy controls (N = 55) using a magnetic resonance imaging (MRI)-based method. A longitudinal MRI scan was acquired in 25 PD patients after a mean follow up period of 12 months.Results: The volume of total body fat as well as of visceral fat showed no difference between PD patients and healthy controls at baseline or at follow up. However, PD patients displayed decreased subcutaneous fat tissue (p = 0.01) and a higher visceral to subcutaneous fat ratio as compared to controls (p = 0.004). After follow up, 16 PD patients did not lose weight, while 9 PD patients lost between 0.5 and 10 kg.Conclusion: Fat distribution is altered in PD patients, with an increased ratio of visceral to subcutaneous fat.
Published: 2016

17. Erratum

Author: Sascha Martens, Masashi Narita, Rajkumar Cheluvappa, Kevin A. Roth, Ta Yuan Chang, Kartik Venkatachalam, Chang-Shen Lin, Sharon G. Adler, Flaminia Pavone, Dianwen Ju, Michelle A. Ozbun, Michael R. Duchen, Shu Feng Zhou, Wei-Guo Zhu, Aaron Di Antonio, Defeng Wu, Taixing Cui, Xu Guang Guo, Zhiping Xie, Lorena García Nannig, Eloy Bejarano, Stéphane D. Lemaire, Petro Starokadomskyy, Hyung Ryong Kim, Mario Pinar, Rebecca T. Marquez, Zvenyslava Husak, Anthony R. White, Joanna Poulton, Antonis S. Zervos, Shweta Sharma, Jochen Walter, Nicholas T. Ktistakis, Christopher H.K. Cheng, Sunhee Lee, Yuen Li Chung, Howard O. Fearnhead, Young J. Oh, Ivano Amelio, Guillermo A. Blanco, Jan Simak, Junfang Wu, Yingying Lu, Mary Kate McBrayer, Soo Han Bae, Ichizo Nishino, Hong-Ming Hu, Benjamin R. Underwood, Tomonori Kimura, Zexian Liu, Savithrama P. Dinesh-Kumar, Qian Yang, Andreas Kern, Hsing Jien Kung, Jan B. Parys, Cam Patterson, Celine Perier, Toshiro Okazaki, Daisuke Koya, Avinash Sonawane, Cédric Cleyrat, Robert I. Richards, Kai Y. Soo, Rodrigo Mora-Rodriguez, Gigi N.C. Chiu, Moon Moo Kim, Vladimir N. Uversky, Shengfang Ge, Matthew T. V. Chan, Irene Kyrmizi, Lara Gibellini, Ángela M. Valverde, Erik Norberg, Fan Zhang, Jan C. Koch, Alec C. Kimmelman, Jingfang Ju, Jie Bai, Lei Duan, Paulina Ordonez, Shuwen Liu, Wolfdieter Springer, Eric Deutsch, Elena Ortona, Jose M. Seguí-Simarro, Vinay Choubey, Leonidas Stefanis, Robert G. Hawley, Claudia Bincoletto, Xian-Hui He, Zhifen Yang, Thomas M. Durcan, Martine Biard-Piechaczyk, Kui Lin, Hongming Pan, Konstantinos Kambas, Cristina Muñoz-Pinedo, Marta Magariños, Yoshinori Takahashi, Adrienne M. Gorman, Philippe Gailly, Takahiko Akematsu, Justine D. Mintern, Liang Xu, Tetsuo Shioi, Luis M. Botana, Yule Liu, Yong Yeon Cho, Jinzhi Lei, Eung Kweon Kim, Alakananda Basu, Vikash Kumar Dubey, Candelaria Gomez-Manzano, Avital Eisenberg-Lerner, Chuan-Ming Xie, Wenjie Dai, Pedro Gonzalez-Alegre, Maria Condello, Zheng-Hong Qin, Zhi-Min Yuan, Catherine Andreadi, Anna Rita Migliaccio, Chong Liu, Michaël Boyer-Guittaut, Melanie Denizot, Esperanza Arias, Greet Van den Berghe, Guomei Tang, Timothy P. Devarenne, Xianyong Sheng, Louis R. Lapierre, J. Wade Harper, Zuzana Storchova, Aileen R. Ariosa, Sug Hyung Lee, Qi Zeng, Godefridus J. Peters, Daniela L. Papademetrio, Alexandre Arcaro, Zhiyuan Yao, Pablo Iribarren, Mario Chiariello, Maria Rosaria Torrisi, Parimal Karmakar, Yong Huang, Sebastiano Sciarretta, Nathalie Andrieu-Abadie, László Fésüs, Patricia Boya, Ruediger Rudolf, Leonor Miller-Fleming, Vasilis J. Promponas, Juan Segura-Aguilar, Paula Daza, Shiow Ju Lee, Songshu Meng, Paul K. Herman, Ludwig Eichinger, Ye-Guang Chen, Kay F. Macleod, Thomas Simmet, Cristina Corral-Ramos, Claudio Brancolini, Jun Ren, Ying Jiang, Benoît Derrien, Xiao Fang Yu, Qing Zhong, Zong Wan Mao, Xingcong Ren, Armando A. Genazzani, Marina Pierdominici, Sanbing Shen, Sandra Moreno, Hana Algül, Maurizio Renna, Ricardo Sánchez-Prieto, Ashok K. Saluja, Yasuo Uchiyama, Pope L. Moseley, Victor E. Dosenko, Chun-Feng Liu, Bakhos A. Tannous, Efthimios Sivridis, Baharia Mograbi, Michiko Shintani, Amanda S. Bess, Rodrigo Portes Ureshino, Avnika A. Ruparelia, Paul Hofman, Eric Chevet, Martha M. Monick, Hong Gang Wang, Daping Fan, Jorge Moscat, Giuseppe Matarese, Consiglia Pacelli, Young Seok Cho, Miriam Cnop, Stefan Böckler, Nikolai V. Gorbunov, Christina J. Sigurdson, Hang T.T. Nguyen, Aurélie François, Katarina Kågedal, Sam Gandy, Silvia Campello, Alain Bruhat, Filomena Fiorito, Hua Feng, Man Tian Mi, Gian Maria Fimia, Masaki Tanaka, Guofei Zhou, José L. Crespo, Heinz Jungbluth, Anna Chiara Nascimbeni, Arianne L. Theiss, Svetlana Dokudovskaya, Mar Lorente, Sergio Lavandero, Yu Xia Zhao, Fangming Lin, Yuchen Feng, Gad Galili, Silvia Cetrullo, Paula I. Moreira, Dhyan Chandra, Dimitrios J. Stravopodis, Roberta A. Gottlieb, Gregory A. Taylor, Longping Wen, Faqiang Li, Marco Sardiello, Umesh K. Jinwal, Francesca Belleudi, Lan Tan, Livia Di Renzo, Tamas Korcsmaros, Xinbing Sui, Douglas R. Green, Guillermo Mazzolini, Hervé Le Stunff, Kelly S. Doran, Mary E. Choi, Carlos S. Subauste, Natalia Rodriguez-Muela, Nicholas J. Talbot, Marta Palmieri, Sonia Hernández-Tiedra, Ligia C. Gomes, Irving M. Shapiro, Makoto Ubukata, Mario P. Tschan, Baris Bingol, Benjamin Loos, Terry Kwok, Luca M. Neri, Sreejayan Nair, Michele Wolfe Bianchi, Ralf Erdmann, Alexander Greenhough, Neeraj Vij, Jeong Hun Kim, Satoaki Matoba, Bo Liu, George R. Beck, Michael Moore, Vrajesh V. Parekh, Kyle A. Bauckman, Li-Lin Du, Mikihiro Fujiya, Yan G. 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Lee, Maria Xilouri, Qi Chen, Claudia Spies, Pengfei Ge, Natascia Ventura, Luca Galluzzi, Yau Hung Chen, Jing Pu Zhang, Diego Albani, Dingzhong Tang, Nikolai Engedal, Stefania Meschini, Maria Lyngaas Torgersen, Shibu M. Poulose, Jean-Paul Decuypere, Ziheng Xu, Jocelyn Laporte, Thierry Arnould, Albert Haas, Ida J. van der Klei, Agustín Hernández, Dong Wook Shin, Per E. Stromhaug, Valentín Ceña, Ugo Pagnini, Karolina Pakos-Zebrucka, Blagovesta Popova, Lisa M Lindqvist, Sangita C. Sinha, Yuguang Shi, Zvonimir Marelja, Robin Candau, Xin Wang, Evelina Gatti, Olatz Pampliega, Michael P. Lisanti, Elena Tamagno, Mei Lan Tan, Gary Warnes, Zdena Palková, Shigeomi Shimizu, Ingo Schmitz, Tino Kurz, Soledad Matus, Gopal Chakrabarti, Joseph J.Y. Sung, Beáta G. Vértessy, Giuliana Cassinelli, Giovanni Benard, Yin Chen, Emma Colucci-Guyon, Craig Blackstone, Lizhi Cao, Sebastian Schuck, Qingqiu Gong, Theocharis Panaretakis, Jayoung Choi, Sven R. 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Heinzen, Xiangmei Chen, Nihal Altan-Bonnet, Sung Sik Lee, Hai Jie Wang, Catherine Dargemont, Jie Du, Sofie Claerhout, Edmond Chan, Yi Sun, Xiangbo Wan, Paul Lingor, Shilpa Buch, Gerald M. McInerney, Zhenlong Wu, Guo Chang Zhang, Iain A. McNeish, Suresh Awale, Mark P. Mattson, Srinivasa Subramaniam, Wuhan Xiao, Katsuhiko Mikoshiba, Giancarlo Parenti, Bruno Miguel Neves, Benjamin Dehay, Fatima Teixeira-Clerc, Patricia Huebbe, Calvin K. Yip, Ryan J. Schulze, Pallabi Sarkar, Vladimir I. Titorenko, Johanna Laukkarinen, Martin E. Gleave, Veronika Stoka, Pascal Genschik, Karen Brown, Zhaoliang Su, Walter Malorni, Arlette Darfeuille-Michaud, Vincent C. O. Njar, Jeffrey E. Pessin, Thomas Wileman, Alexander J. Whitworth, Stefano Santaguida, Gustavo A. Nader, Gláucia Maria Machado-Santelli, Marie-Josée Hébert, Skye C. McIver, Scott A. Soleimanpour, Jia-Hong Lu, Fei Liu, Yu Wang, Elisa Motori, Chad A. 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Kumar, Deok Ryong Kim, Jianjie Ma, Sang Won Suh, Guido Kroemer, Klára Megyeri, Michael N. Sack, Heinrich Taegtmeyer, Gilles Pagès, Gabriella Marfe, Gregg L. Semenza, Karine G. Le Roch, Marisa Brini, Marina Bouché, Oliver Kepp, Vinay V. Eapen, J. David Beckham, Stephan T. Stern, Xudong Zhang, Marcello Pinti, Xiangnan Zhang, Jae Keun Lee, Ana Coto-Montes, Assaf Rudich, Laura D. Attardi, Debabrata Ghosh, Philip Rosenstiel, Sébastien Besteiro, Maria Rosa Sarrias, R. Andres Floto, Xiao Ming Yin, Nicholas W. Lukacs, Hermann Pavenstädt, Matias Simons, Hitoshi Nakatogawa, Sandro Alves, Krisztina Takács-Vellai, Masato Koike, Debasish Sinha, Shoji Notomi, Faraj Terro, Maria Carmela Roccheri, Santiago Ambrosio, K. Ulrich Bayer, Yumin Li, Terje Johansen, Christian Kuhn, Yee Shin Lin, David C. Rubinsztein, Ziwei Qu, Ronit Shiri-Sverdlov, Emmanuel T. Akporiaye, Galila Agam, Hui Ling Chiang, Seung-Jae Lee, Yu Xue, Francesca Giampieri, Markus Damme, Tassula Proikas-Cezanne, Tianwei Lin, Marc Kantorow, Guang-Chao Chen, Qiangrong Liang, Claudia Manzoni, Joan S. Steffan, Emilio Boada-Romero, Damien Freyssenet, Sepp D. Kohlwein, Maria D. Barrachina, Yulin Liao, Jiankang Chen, Erika Isono, Hugo Seca, Mei Wang, Taras Y. Nazarko, Yannick Bailly, Nadya V. Koshkina, Tapas K. Maiti, Bärbel Rohrer, Karin Nowikovsky, James H. Hurley, Gerald W. Dorn, Nils C. Gassen, Kazuhiro Nagata, Eiki Kominami, A. Ivana Scovassi, Ana Maria Cuervo, Adi Kimchi, Minghua Yang, Sylviane Muller, Life Sciences Institute and Department of Molecular, Cellular, and Developmental Biology and Biological Chemistry, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Defense in Plant-Pathogen Interactions [Nagoya, Japan], Nagoya University-Graduate School of Bioagricultural Sciences [Nagoya, Japan], Facultad de Quimica [Santiago], Pontificia Universidad Católica de Chile (UC), Institute of Cancer Sciences [Glasgow, UK] (CR-UK Beatson Institute), University of Glasgow, Cell Death Research & Therapy (CDRT) Lab, Université Catholique de Louvain, Harvard University Statistics Department, Harvard University [Cambridge], Centre épigénétique et destin cellulaire (EDC (UMR_7216)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Conway Institute of Biomolecular and Biomedical Research and School of Chemical and Bioprocess Engineering, University College Dublin [Dublin] (UCD), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biochemistry and Molecular Biology, Thomas Jefferson University-Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University)-Jefferson (Philadelphia University + Thomas Jefferson University), Centro de Estudios Farmacológicos y Botánicos [Buenos Aires] (CEFYBO), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA), Thérapie génique, Génomique et Epigénomique (U 1169), Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Department of Experimental Medicine and Public Health, University of Camerino, MRC Toxicology Unit, University of Leicester, Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Departamento de Bioquímica y Biología Molecular y Celular, University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pharmaco-Biology, Università della Calabria [Arcavacata di Rende] (Unical), Department of Molecular Genetics [Rehovot, Israël], Weizmann Institute of Science, Fondation Universitaire Notre Dame de la Paix (FUNDP), Facultés Universitaires Notre-Dame de la Paix, Département Advanced Research And Techniques For Multidimensional Imaging Systems (ARTEMIS), Institut Mines-Télécom [Paris] (IMT)-Télécom SudParis (TSP), USC Neuromuscular Center, Department of Neurology, University of Southern California (USC), Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Giannina Gaslini Institute, Department of Molecular Pharmacology, Albert Einstein College of Medicine, Department of Cancer Biology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Institut des Sciences de l'Evolution de Montpellier (UMR ISEM), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-École pratique des hautes études (EPHE)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226-Centre National de la Recherche Scientifique (CNRS), Inner Mongolia Agricultural University (IMAU), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Indian Institute of Science [Bangalore] (IISc Bangalore), Politecnico di Milano [Milan] (POLIMI), Département des Sciences Biologiques [Montréal], Université du Québec à Montréal (UQAM), Laboratory of Molecular Biology, Scientific Institute E. Medea, Université Catholique de Louvain (UCL), Univ Ancona, Politecn Marche, University of Toronto, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Department of Clinical and Molecular Medicine, Università degli Studi di Roma 'La Sapienza' [Rome]-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Hémato-Cancérologie Expérimentale, CRP-Santé, Dpt of Neuroscience and Brain Technologies [Genova], NeuroEngineering & bio-arTificial Synergic SystemS Laboratory [Genova] (NetS3 Lab), Istituto Italiano di Tecnologia (IIT)-Istituto Italiano di Tecnologia (IIT), Center for Infection and Immunity Amsterdam (CINIMA), Laboratoire de biogenèse membranaire (LBM), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Régulation de l'expression génétique (REG), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology and Immunology, Stanford University School of Medicine [CA, USA], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Dermatology, Brigham and Women's Hospital [Boston], San Raffaele Scientific Institute, Milan, Italy, Laboratory of Molecular Neuroembryology, University of Rome 'Tor Vergeta'-Clinical and Behavioral Neurology - Neuroscienze e riabilitazione, IRCCS Fondazione Santa Lucia [Roma]-Dulbecco Telethon Institute, Department of Pharmacology, Universidade de Santiago de Compostela, Glycobiologie et signalisation cellulaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Complexo Hospitalario Universitario A Coruña, Mécanismes moléculaires de l'angiogénèse, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Florida [Gainesville], Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer (JPArc - U1172 Inserm), Université Lille Nord de France (COMUE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université Lille 2 - Faculté de Médecine, Centro de Investigaciones Biológicas (CSIC), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Infection bactérienne, inflammation, et carcinogenèse digestive, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Universita degli Studi di Padova, University of British Columbia (UBC), University of Edinburgh, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Australian Regenerative Medicine Institute, Monash University, Clayton, 3800, VIC, Australia, Faculty of Engineering and Natural Sciences, Sabanci University [Istanbul], Department of Biological Sciences [Stanford], Stanford University [Stanford], Université de Montréal (UdeM), Department of Human Genetics, Department of Psychiatry, University of Michigan System-University of Michigan System-Molecular and Behavioral Neuroscience Institute, Centre for Computational and Systems Biology (COSBI), Department of Computer Science [Tsukuba], Graduate School of Systems and Information Engineering [Tsukuba], University of Tsukuba-University of Tsukuba, Institut de biochimie et génétique cellulaires (IBGC), University of Western Ontario (UWO), Genetics, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Department of Biochemistry and Biophysics, University of Naples Federico II, Lund University [Lund], Institute of Molecular Biosciences, Karl-Franzens University Graz, (IMB), Karl-Franzens-Universität Graz, Polytechnic University of Marche, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Cell Biology, Physiology and Immunology, Research Unit on BioActive Molecules, Departamento de Química Orgánica Biológica, Instituto de Investigaciones Quimicas y Ambientales de Barcelona, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), The Buck Institute for Age Research, University of Pisa - Università di Pisa, Laboratorio di Genetica Molecolare, Istituto Gaslini, Universidad de Castilla-La Mancha (UCLM), Laboratoire de Biologie Moléculaire et Cellulaire du Cancer, Hôpital Kirchberg, University of Crete [Heraklion] (UOC), Division of Molecular and Cellular Pathology [Birmingham], Department of Medical Research, Taichung Veterans General Hospital, Modélisation et Simulation Numérique en Mécanique et Génie des Procédés (MSNMGP), Université de la Méditerranée - Aix-Marseille 2-Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), University of Queensland [Brisbane], Dept of Mathematics, Purdue University, Purdue University [West Lafayette], Virologie et Pathologie Humaine (VirPath), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Zhejiang University, Équipe Micro et nanosystèmes HyperFréquences Fluidiques (LAAS-MH2F), Laboratoire d'analyse et d'architecture des systèmes (LAAS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse 1 Capitole (UT1)-Université Toulouse - Jean Jaurès (UT2J), King Abdullah University of Science and Technology (KAUST), Southern University of Science and Technology of China (SUSTech), OASE, National University of Tainan, Taiwan (OASE), National Taiwan University [Taiwan] (NTU), Weifang Bureau of Land Resources [Weifang], Department of cardiology [Guy's and St. Thomas ' hospitals] [London], Guy's and St Thomas' Hospital [London]-Guy's Hospital [London], University of Pennsylvania [Philadelphia], CRLCC Eugène Marquis (CRLCC), Emory University School of Medicine, Emory University [Atlanta, GA], Korea University, Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pharmacology [Tartu, Estonie], Institute of Biomedicine and Translational Medicine [Tartu, Estonie], University of Tartu-University of Tartu, Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Max-Planck-Gesellschaft, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Cincinnati (UC), Réponses immunes : régulation et développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Experimental Medicine, Oxford University, University of Oxford [Oxford], Division of regenerative Medicine, San Raffaele Scientific Institute, The University of New Mexico [Albuquerque], Université Libre de Bruxelles [Bruxelles] (ULB), Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU)-Johns Hopkins University (JHU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Scienze Biomediche, Università degli Studi di Modena e Reggio Emilia (UNIMORE), Department of Experimental Medicine and Oncology, University of Turin, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), CNV, University of Valparaiso, Institut Gustave Roussy (IGR), Universidad Autonoma de Madrid (UAM), Cell Signalling & Proteomics Group [Londres, Royayme-Uni], Barts Cancer Institute [Londres, Royayme-Uni], Queen Mary University of London (QMUL)-Queen Mary University of London (QMUL), Department of General, Visceral and Vascular Surgery [Jena], Friedrich-Schiller-Universität Jena, Department of Biomedical Engineering, The University of Texas at Austin, University of Texas at Austin, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Fondazione Santa Lucia (IRCCS), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jacques Monod (IJM (UMR_7592)), Institute of Biological, Environmental and Rural Sciences (IBERS), Aberystwyth University, Department of Biology, Johns Hopkins University (JHU), Neurogenetics Group, Instituto de Investigación en Recursos Cinegéticos (IREC), Laboratório de Ultraestrutura Celular Hertha Meyer (IBCCF), Universidade Federal do Rio de Janeiro [Rio de Janeiro] (UFRJ), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Molecular and Cellular Biology, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), National University of Ireland [Galway] (NUI Galway), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Freiburg Institute for Advanced Studies-LifeNet, Albert-Ludwigs-Universität Freiburg, Groupe de Recherche en Immunopathologies et maladies infectueuses (GRI), Université de La Réunion (UR)-Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Brunel University London [Uxbridge], Unité Propre de Recherche 2357, Institution de Biologie Moléculaire des Plantes, Radiothérapie moléculaire (UMR 1030), Department of Chemistry, University of Kentucky, Universidad de Córdoba [Cordoba], Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' [Rome], Facultad de Ciencias Químicas y Farmacéuticas, Centro de Estudios Moleculares de la Célula, Biochemistry and Molecular Biology, Goethe-University Frankfurt am Main, Department of Biological and Environmental Sciences and Technologies (DiSTeBA), Università del Salento, Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Institut National Polytechnique de Lorraine (INPL), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Institut de recherches sur la catalyse et l'environnement de Lyon (IRCELYON), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Européen de Chimie et Biologie (IECB), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Trafic membranaire et Division cellulaire, Landesbetrieb Hessisches Landeslabor, Hematology-Oncology Division, Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], University of Pavia, Instituto de Investigaciones Biotecnológicas [San Martín] (IIB-INTECH), Universidad Nacional de San Martin (UNSAM)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), University of Helsinki, School of Physics and Astronomy [Exeter], University of Exeter, Department of Biomedicinal Chemistry (CSIC), Institut de Química Avançada de Catalunya, Laboratory of Vascular Pathology (IDI-IRCCS), Istituto Dermopatico dell'Immacolata, Peking University [Beijing], MRC Centre for Developmental Neurobiology, University of Brescia, Immunobiologie fondamentale et clinique, Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), University of Rome 'Tor Vergeta', Universidad de Oviedo [Oviedo], Laboratoire des signaux et systèmes (L2S), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Dulbecco Telethon Institute/Department of Biology, Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Rockefeller University [New York], The Babraham Institute, Kansas State University, McGill University, Service d'Anatomie et Cytologie Pathologique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Department of Medicine [New York], Icahn School of Medicine at Mount Sinai [New York] (MSSM), ATOS Origin, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences-Tohoku University [Sendai], Goethe-University, Goethe-Universität Frankfurt am Main, Institute of physiological chemistry, Hannover Medical School [Hannover] (MHH), Department of Physiology, Department of Plant and Environmental Sciences, Apoptose, cancer et immunité (U848), Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Departments of Neurology and Psychiatry, Alzheimer's Disease Research Center, Institute of Experimental Immunology - IEI [Zürich, Switzerland], Université de Zurich [Switzerland], Digital Enterprise Research Institute (DERI-NUIG), Spanish National Research Council (CSIC), Cell Death Research and Therapy Unit [Leuven, Belgium] ( Department of Cellular and Molecular Medicine), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Signaling in Oncogenesis, Angiogenesis and Permeability - SOAP (CRCINA - Département ONCO - Equipe 15), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Department of Medicine [San Francisco], University of California [San Francisco] (UCSF), University of California-University of California, Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Department of Anatomy, Histology, Forensic Medicine and Orthopedic, N.A., Division of Pharmacology and Chemotherapy, Department of Internal Medicine, Pathogénie Microbienne Moléculaire, University of Chile [Santiago], Université de Montpellier (UM), Faculdade de Ciências Farmacêuticas de Ribeirão Preto [São Paulo], Universidade de São Paulo (USP), Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Institut de recherche en cancérologie de Montpellier (IRCM - U896 Inserm - UM1), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Catalan Institute of Oncology, Department of Cell Biology, National Institute for Basic Biology [Okazaki], Instituto de Bioquímica Vegetal y Fotosíntesis (IBVF), Universidad de Sevilla-Centro de Investigaciones Científicas Isla de la Cartuja, The Adams Super Center for Brain Studies, Tel Aviv University [Tel Aviv], Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), Department of Pharmacology and biochemistry, Virginia Commonwealth University (VCU), Department of Immunology, St Jude Children's Research Hospital, Department of Biology and Biotechnologies 'Charles Darwin', Lettres, Idées, Savoir (LIS), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute of Biological Chemistry and Nutrition, University of Hohenheim, China Seismological Bureau, Massachusetts Institute of Technology (MIT), Rosenstiel Basic Medical Sciences Research Center [Waltham], Brandeis University, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Meakins-Christie Laboratories, Sanford Burnham Medical Research Institute, La Jolla, National Institute of Advanced Industrial Science and Technology (AIST), ORIENT ET MÉDITERRANÉE : Textes, Archéologie, Histoire (OM), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Centro de Investigacion y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV), Biochemistry and Molecular Biology I, Department of Immunology and Infectious Diseases, Harvard School of Public Health, aDepartment of Plant Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences (SLU), Philipps University of Marburg, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Renal Division, University Medical Center Freiburg, Freiburg, Germany, Rural Health Academic Centre, University of Melbourne-Rural Clinical School, Department of Pathology, University of Veterinary and Animal Sciences, Dipartimento di Scienze della Vita [Modena, Italy], Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology, Anatomy & Cell Biology [Philadelphia, Pennsylvania, USA], Thomas Jefferson University, Department of Molecular Neuroscience, Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Centro de Investigación en Bioquímica Clínica e Inmunología (CONICET), Universidad Nacional de Córdoba, Córdoba, Argentina, Neuroinflammation Unit, Biotech Research and Innovation Centre-University of Copenhagen = Københavns Universitet (KU), Mathematics and Computing in Automatic Control and Optimization for the User (MIAOU), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Danish Cancer Society, Institute of Cancer Biology, UCL-Institute of Child Health (ICH), Institute of Child Health-Great Ormond Street Hospital for Children [London] (GOSH), Division of Renal Diseases and Hypertension, University of Colorado [Boulder], Institut de biologie et chimie des protéines [Lyon] (IBCP), Joslin Diabetes Center, Universität Ulm - Ulm University [Ulm, Allemagne], Qingdao Institute of Marine Geology, China Geological Survey, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Institute of Software, Chinese Academy of Sciences [Beijing] (CAS), Metabolic Engineering Group, Departamento de Microbiologia y Genetica, Edificio Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, University of Minnesota [Twin Cities], University of Minnesota System, Department of Cellular and Molecular Physiology, Yale University School of Medicine, The Arctic University of Norway, Department of Biological Sciences, The Open University [Milton Keynes] (OU), Summit Analytical, CALRG, Institute of Educational Technology, Institute for Neurologic Disabilities Research, Faculty of Health Sciences-University of Pretoria [South Africa], Department of Paediatric Neurology, Guy's and St Thomas' Hospital [London]-Evelina Children's Hospital, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Dana-Farber Cancer Institute and the Department of Cell Biology, Harward Medical School, Translational Health Science and Technology Institute [Faridabad] (THSTI), Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, School of Reliability and Systems Engineering [Beijing], Beihang University, Oxford Centre for Integrative Systems Biology, Center for Membrane and Cell Physiology [Charlottesville, VA, USA] (School of Medicine), University of Virginia [Charlottesville], Apoptose, cancer et immunité (Equipe labellisée Ligue contre le cancer - CRC - Inserm U1138), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Karlsruher Institut für Technologie (KIT), Faculty of Pharmaceutical Sciences, Hokkaido University, École normale supérieure - Paris (ENS Paris), School of Electrical Engineering [Seoul] (Korea University), Department of Mathematics and Statistics [Guelph], University of Guelph, Department of Molecular Genetics, Department of Genetics [Stanford, CA, États-Unis], Institute of Immunology, University Hospital Schleswig-Holstein, Arizona Respiratory Center, Okazaki Institute for Integrative Bioscience, ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Newcastle University [Newcastle], JRC Institute for Transuranium Elements [Karlsruhe] (ITU ), European Commission - Joint Research Centre [Karlsruhe] (JRC), Department of Neuroscience, University of Texas Southwestern Medical Center [Dallas], Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Laboratory of Functional Neurogenomics [Tuebingen, Germany], University of Tuebingen-Center of Neurology and Hertie-Institute for Clinical Brain Research [Tuebingen, Germany], Indian Institute of Technology Bombay (IIT Bombay), European Organization for Nuclear Research (CERN), Harvard Medical School [Boston] (HMS), Indian School of Mines, Department of Computer Science [UIUC] (UIUC), University of Illinois at Urbana-Champaign [Urbana], University of Illinois System-University of Illinois System, Centre for Cancer Biology, Hanson Institute, Adelaide, University of California [San Diego] (UC San Diego), University of California, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Biochemistry, University of Bristol, Organisation Nucléaire et Oncogenèse, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), FONDAP Center CEMC Estudios Moleculares de la Célula, Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Chungnam National Univesity School of Medicine, Taejon, Korea, Chungnam National Univesity School of Medicine, Micro & Nanobiotechnologies, Institut des Sciences Analytiques (ISA), Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de génétique moléculaire (CGM), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Center for Applied Mathematics, Tsinghua University [Beijing], University of Connecticut School of Medicine, University of Connecticut (UCONN), Laboratoire de Biologie Moléculaire et Cellulaire des Eucaryotes (LBMCE), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Microenvironnement et Physiopathologie de la Differenciation, Division of Nephrology and Hypertension, Mayo Clinic, Beatson Institute for Cancer Research, Beatson institute for cancer research, Howard Hughes Medical Institute, Howard Hugues Medical Institute, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Computing Technology [Beijing] (ICT), Chinese Academy of Sciences [Changchun Branch] (CAS), School of Electronics and Computer Science (ECS), University of Southampton, Third Hospital, Department of Anesthesiology, Cognitive Interaction Technology [Bielefeld] (CITEC), Universität Bielefeld = Bielefeld University, Procédés, Matériaux et Energie Solaire (PROMES), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Faculty of Pharmacy- University of Coimbra, National Neuroscience Institute, Key Laboratory of Molecular Virology & Immunology (LMVI), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Coll Life Sci, Beijing Normal University, Delft University of Technology (TU Delft), Christian-Albrechts-Universität zu Kiel (CAU), Department of Molecular Pathology and Microbiology, Center for Applied Proteomics and Molecular Medicine-George Mason University [Fairfax], Sidney Kimmel Cancer Center, Jefferson (Philadelphia University + Thomas Jefferson University), Institut des Sciences Chimiques de Rennes (ISCR), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Department of Chemistry, University of Pittsburgh, University of Pittsburg, Tianjin University of Science and Technology (TUST), Hunan University of Science and Technology [Xiangtan], Laboratoire de Génie Civil et Génie Mécanique (LGCGM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), China Agricultural University (CAU), Acad Disaster Reduct and Emergency Management, Minist Civil Affairs, Minist Educ, Beijing, Peoples R China, affiliation inconnue, Département Technologie des Polymères et Composites & Ingénierie Mécanique (TPCIM), École des Mines de Douai (Mines Douai EMD), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Ministère de l'Economie, des Finances et de l'Industrie, MOE Key Laboratory of Bioinformatics, Centre for Plant Biology, School of Life Sciences, Laboratoire d'Informatique Gaspard-Monge (ligm), Université Paris-Est Marne-la-Vallée (UPEM)-École des Ponts ParisTech (ENPC)-ESIEE Paris-Fédération de Recherche Bézout-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie Moléculaire et Cellulaire (LBMC), Université de Bourgogne (UB), Center for International Blood and Marrow Transplant Research (CIBMTR), Emory University [Atlanta, GA]-Medical College of Wisconsin, Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Illman Cancer Center, Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Ingénierie des Matériaux Polymères (IMP), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA), Department of Medical Microbiology and Immunology, University of California [Davis] (UC Davis), School of Health Sciences, University of Minho [Braga], Équipe Calcul Distribué et Asynchronisme (LAAS-CDA), University of California [Riverside] (UCR), Ohio State University [Columbus] (OSU), Laboratory of Systems Biology, Van Andel Institute [Grand Rapids], Division of Genetics and Cell Biology, National Center for Gender-Specific Medicine, Istituto Superiore di Sanità, Oregon Health and Science University [Portland] (OHSU), Dendrite Differenciation Group [DZNE - Bonn], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Equipe 12, Génétique moléculaire, signalisation et cancer (GMSC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Medical Center [Utrecht], Institut d'Investigacions Biomèdiques August Pi I Sunyer [Barcelona, Spain] (Hospital Clinic ), Department of Genetics, Trinity College Dublin, Fisiopatologia de los procesos inflamatorios, Vall d'Hebron Research Institute, Institució Catalana de Recerca i Estudis Avançats (ICREA), Department of Human Genetics, Nagasaki University, Transduction du signal et oncogénèse, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie, Center for Experimental and Molecular Medicine, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Department of medical Biochemistry, University of Amsterdam [Amsterdam] (UvA), IDI-IRCCS Biochemistry Laboratory, Università degli Studi di Roma Tor Vergata [Roma], Program Against Cancer Therapeutic Resistance/Metabolism & Cancer Group [Catalonia, Spain] (ProCURE), Catalan Institute of Oncology-Girona (ICO-Girona), Instituto de Tecnologia Química e Biológica António Xavier (ITQB), Universidade Nova de Lisboa (NOVA), Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza Hospital, CNR, Consiglio Nazionale delle Ricerche (CNR), Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute, The Hospital for sick children [Toronto] (SickKids), Universidad de Sevilla, Immunité muqueuse et vaccination, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR50-Université Nice Sophia Antipolis (... - 2019) (UNS), DIMS, University of Trento [Trento], Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Department of Cellular and Molecular Medicine [Madrid, Spain], Laboratory of Cell Death and Cancer Therapy [Madrid, Spain], Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC) -Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3HD, UK, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dpt. of Cancer & Cell Biology, Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Max planck Institute for Biology of Ageing [Cologne], Euromov (EuroMov), Wellcome Trust Centre for Molecular Parasitology [Glasgow, UK], University of Glasgow- Institute of Infection, Immunity and Inflammation [Glasgow, UK], Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), UMR 1599, Centre National de la Recherche Scientifique (CNRS), EA 4100, Histoire culturelle et sociale de l'art (HiCSA), Université Panthéon-Sorbonne (UP1)-Université Panthéon-Sorbonne (UP1), Centre for Astrophysics and Supercomputing (Centre for Astrophysics and Supercomputing), Swinburne University of Technology [Melbourne], Department of Cellular and Physiological Sciences [Vancouver, BC, Canada] (Life Sciences Institute), University of British Columbia (UBC)-Life Sciences Institute [Vancouver, BC, Canada], School of Pharmacy, Department of Experimental Medicine, Dept. Neurosciences, Department of Internal Medicine, Radboud University Medical Center [Nijmegen], Institute of Medical Genetics and Applied Genomics, Radiation Physics, School of Life Science, Department of Basic Biology, The Graduate University for Advanced Studies, CIBER de Enfermedades Neurodegenerativas (CIBERNED), Doshisha University, National Cancer Research Center [Tokyo, Japan], University of Washington [Seattle], Department of Experimental Neurodegeneration [Göttingen, Germany], University Medical Center Göttingen (UMG), Cibles moléculaires et thérapeutiques de la maladie d'Alzheimer (CIMoTHeMA), Université de Poitiers, Laboratoire de Probabilités et Modèles Aléatoires (LPMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), BioCeV-Institute of Microbiology, Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto di chimica biologica, Università degli Studi di Verona, Département Image et Traitement Information (ITI), Institut Mines-Télécom [Paris] (IMT)-Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne, Department of Cell Biology and Biophysics, Università degli Studi di Firenze [Firenze], Cell Immunity in Cancer, Inflammation and infection Group [Zaragoza, Spain] (Biomedical Research Center), Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain]-University of Zaragoza - Universidad de Zaragoza [Zaragoza], Department of Pediatrics, Università degli studi di Napoli Federico II, Transfert de Genes a Visee Therapeutique Dans les Cellules Souches, Developpement Normal et Pathologique du Système Immunitaire, Signalisation et physiopathologie des cellules épithéliales, Facultad de Medicina, Universidad de Santiago de Chile [Santiago] (USACH), Departamento de Farmacobiología, Cinvestav-Sede Sur, Centre de recherche Croissance et signalisation (UMR_S 845), College of Life Sciences, Central China Normal University, Institute of Molecular Biotechnology, Austrian Academy of Sciences (OeAW), Laboratory of Cardiac Surgical Research, Monash University [Clayton], Universidade do Minho, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Neurodegenerative Diseases Research Group (CIBERNED), Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases, Barcelona, Department of medicine, Syracuse, NY, USA, State University of New York (SUNY), National University of Singapore (NUS)-Yong Loo Lin School of Medicine-Graduate School for Integrative Sciences and Engineering, McGill University Health Center [Montreal] (MUHC), National Institute for Infectious Diseases, Transporteurs en Imagerie et Radiothérapie en Oncologie (TIRO - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut Gustave Roussy (IGR)-Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biomedical Sciences, Department of Genetics of Eukaryotic Microorganisms, Georg-August-University [Göttingen]-Institute of Microbiology and Genetics, Sterol metabolism and therapeutic innovations in oncology, Institut Claudius Regaud, CRLCC Institut Claudius Regaud-CRLCC Institut Claudius Regaud-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Department of Molecular, Cellular and Developmental Biology, Señalización Celular 4, Institute of integrative biology (Liverpool), University of Liverpool, Department of Human Biology, University of Cape Town, National Institute of Diabetes and Digestive and Kidney Diseases [Bethesda], Department of Molecular Biology, Eberhard Karls Universität Tübingen, Technical University of Munich (TUM), Biophysics and Bioinformatics Laboratory, Department of Cell Biology and Morphology, Université de Lausanne (UNIL), Shenyang Institute of Automation, the Chinese Academy of Sciences (SIA), Key Laboratory of Thermo-Fluid Science and Engineering of Ministry of Education, Xi'an Jiaotong University (Xjtu), Dipartimento di Biologia, Mechanics laboratory , UniversityAmar Telidji, 3000 Laghouat, Algéria., Mechanics laboratory , University Amar Telidji, sans affiliation, Service d'hépatologie [Hôpital Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), University of Waterloo, Waterloo, ON, Canada, Institute of Cell Biology and Immunology, University of Stuttgart, Chaperones Research Group, Institute of Biosciences and Technology [Houston, TX, États-Unis] (IBT), Texas A&M Health Science Center [Houston, TX, États-Unis] (TAMHSC), Texas A&M University Health Science Center-Texas A&M University Health Science Center, Aquatic and Crop Resource Development, National Research Council of Canada (NRC), Cibles thérapeutiques, formulation et expertise pré-clinique du médicament (CITHEFOR), Université de Lorraine (UL), Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche [Ancona] (UNIVPM), Department of Biochemistry and Molecular Biology [Indianapolis, IN, USA], Indiana University School of Medicine, Indiana University System-Indiana University System, Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, iMed.UL, Faculty of Pharmacy, University of Lisbon, CESAM & Biology Department, Universidade de Aveiro, Celullar and Molecular Medicine, Università degli Studi di Perugia (UNIPG), Institute of Clinical Molecular Biology, Kiel University, Apoptose et Système Immunitaire (ASI), Vieillissement Cellulaire Intégré et Inflammation (VCII), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematical Sciences [Aalborg], Aalborg University [Denmark] (AAU), Cambridge Institute for Medical Research (CIMR), University of Cambridge [UK] (CAM), Biozentrum, University of Basel (Unibas), Structural and Computational Biology Unit, European Molecular Biology Laboratory [Grenoble] (EMBL), Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers), Université de Perpignan Via Domitia (UPVD), Universidad Pablo de Olavide [Sevilla] (UPO), Department of Neurosciences, Agronomes et Vétérinaires Sans Frontières (AVSF), AVSF, Department of Mathematics [Gakushuin], Gakushuin University, Department of Internal Medicine [Münster, Germany], University of Münster, Neurogenetics laboratory, University Medicine Goettingen, Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université d'Uruguay, Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Institute for Conservation & Improvement of Valentian Agrodiversity (COMAV), Universitat Politecnica de Valencia (UPV), ICBM, University of Chile [Santiago]-Faculty of Medicine, Nutrition, Métabolisme, Aquaculture (NuMéA), Institut National de la Recherche Agronomique (INRA)-Université de Pau et des Pays de l'Adour (UPPA), Department of Cell Biology, Baltimore, Johns Hopkins University School of Medicine, Baylor College of Medicine (BCM), Baylor University, University of Minnesota Medical School, Beijing Candid soft Technology Co. Ltd, Nanjing University of Information Science and Technology, Department of Hepatobiliary and Pancreatic Surgery [Maebashi, Japan], Gunma University Graduate Schoolof Medicine [Maebashi, Japan], Department of Molecular Genetics [Maastricht, The Netherlands], Maastricht University [The Netherlands], Institute of Cell Biology and Genetic Engineering, National Academy of Sciences of Ukraine (NASU), Institute of Pharmacology of Natural Products and Clinical Pharmacology, Institute of Pharmacology, University of Bern, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Wilmer Eye Institute, Mayo Clinic and Mayo College of Medicine, Rochester, Institute of Biochemistry and Biophysics, Polska Akademia Nauk (PAN)-Sciences, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Chemistry and Toxicology, Norwegian Veterinary Institute, Department of Gynecologic Oncology, The University of Texas M.D. Anderson Cancer Center [Houston], University of Minho, Friedrich Miescher Laboratory (FML), Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Department of Biomedical Sciences and Biotechnologies, Brescia University, Department of Physiological Chemistry [Bochum], Ruhr-Universität Bochum [Bochum], University of Oslo (UiO), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Facultés Universitaires Notre Dame de la Paix (FUNDP), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut de recherche pour le développement [IRD] : UR226, Université du Québec à Montréal = University of Québec in Montréal (UQAM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Université Lille 2 - Faculté de Médecine -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Lille Nord de France (COMUE)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon), Institut de Chimie de Toulouse (ICT-FR 2599), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse 1 Capitole (UT1)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Université libre de Bruxelles (ULB), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Rio de Janeiro (UFRJ), Institut Bergonié [Bordeaux], UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Trafic membranaire et Division cellulaire - Membrane Traffic and Cell Division, Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-Université Paris-Sud - Paris 11 (UP11), McGill University = Université McGill [Montréal, Canada], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Signaling in Oncogenesis, Angiogenesis and Permeability (CRCINA-ÉQUIPE 15), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Universidad de Chile = University of Chile [Santiago] (UCHILE), Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III (ISC), Université Montpellier 1 (UM1)-CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Université Panthéon-Sorbonne (UP1)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Collège de France (CdF (institution)), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, Hokkaido University [Sapporo, Japan], Université Paris sciences et lettres (PSL), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Lyon-Université de Lyon, Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Organisation Nucléaire et Oncogenèse - Nuclear Organization and Oncogenesis, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Centre National de la Recherche Scientifique (CNRS)-Institut de biologie physico-chimique (IBPC (FR_550)), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU), The Beatson Institute for Cancer Research, Beijing Normal University (BNU), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Fédération de Recherche Bézout-ESIEE Paris-École des Ponts ParisTech (ENPC)-Université Paris-Est Marne-la-Vallée (UPEM), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Université de Lyon-Université de Lyon-Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon], Vall d’Hebron Research Institute (VHIR), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Universidade Nova de Lisboa = NOVA University of Lisboa (NOVA), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Doshisha University [Kyoto], Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT), Università degli Studi di Firenze = University of Florence [Firenze], University of Zaragoza - Universidad de Zaragoza [Zaragoza]-Nanoscience Institute of Aragon - INA [Zaragoza, Spain]-Fundación Agencia Aragonesa para la Investigación y el Desarrollo - ARAID [Zaragoza, Spain], Central China Normal University [Wuhan, China], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de biologie structurale [1992-2019] (IBS - UMR 5075 [1992-2019]), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Nanjing University of Information Science and Technology (NUIST), Facultad de Medicina [Buenos Aires], Universidad de Buenos Aires [Buenos Aires] (UBA)-Universidad de Buenos Aires [Buenos Aires] (UBA)-Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Clermont Auvergne (UCA)-Institut National de la Recherche Agronomique (INRA), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)-Universidad Nacional de San Martin (UNSAM), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, George Mason University [Fairfax]-Center for Applied Proteomics and Molecular Medicine, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institute of Infection, Immunity and Inflammation [Glasgow, UK]-University of Glasgow, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Settore BIO/06, biology, Cell Biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, biology.organism_classification, Cell biology, Interpretation (model theory), 03 medical and health sciences, Arama, 030104 developmental biology, Molecular Biology, Humanities, ComputingMilieux_MISCELLANEOUS
Abstract: Author(s): Klionsky, DJ; Abdelmohsen, K; Abe, A; Abedin, MJ; Abeliovich, H; Arozena, AA; Adachi, H; Adams, CM; Adams, PD; Adeli, K; Adhihetty, PJ; Adler, SG; Agam, G; Agarwal, R; Aghi, MK; Agnello, M; Agostinis, P; Aguilar, PV; Aguirre-Ghiso, J; Airoldi, EM; Ait-Si-Ali, S; Akematsu, T; Akporiaye, ET; Al-Rubeai, M; Albaiceta, GM; Albanese, C; Albani, D; Albert, ML; Aldudo, J; Algul, H; Alirezaei, M; Alloza, I; Almasan, A; Almonte-Beceril, M; Alnemri, ES; Alonso, C; Altan-Bonnet, N; Altieri, DC; Alvarez, S; Alvarez-Erviti, L; Alves, S; Amadoro, G; Amano, A; Amantini, C; Ambrosio, S; Amelio, I; Amer, AO; Amessou, M; Amon, A; An, Z; Anania, FA; Andersen, SU; Andley, UP; Andreadi, CK; Andrieu-Abadie, N; Anel, A; Ann, DK; Anoopkumar-Dukie, S; Antonioli, M; Aoki, H; Apostolova, N; Aquila, S; Aquilano, K; Araki, K; Arama, E; Aranda, A; Araya, J; Arcaro, A; Arias, E; Arimoto, H; Ariosa, AR; Armstrong, JL; Arnould, T; Arsov, I; Asanuma, K; Askanas, V; Asselin, E; Atarashi, R; Atherton, SS; Atkin, JD; Attardi, LD; Auberger, P; Auburger, G; Aurelian, L; Autelli, R
Published: 2016

18. Muscle gene expression is a marker of amyotrophic lateral sclerosis severity

Author: Philippe Demougin, Marc de Tapia, Luc Dupuis, Timothée Lenglet, Odile Dubourg, Jean-Christophe Corvol, François Salachas, Vincent Meininger, Michael Primig, Jean-Philippe Loeffler, Pierre-François Pradat, Gaëlle Bruneteau, Jose-Luis Gonzalez de Aguilar, Franck Di Scala, Lucette Lacomblez, Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Biozentrum [Basel, Suisse], University of Basel (Unibas), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Neuropathologie Raymond Escourolle [CHU Pitié-Salpétriêre], Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], and Biozentrum
Subjects: Male, Pathology, MESH: Genetic Markers, Manual Muscle Testing, 0302 clinical medicine, Degenerative disease, Myocyte, Amyotrophic lateral sclerosis, MESH: Amyotrophic Lateral Sclerosis, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Deltoid Muscle, Middle Aged, MESH: Gene Expression Regulation, MESH: Case-Control Studies, Muscle atrophy, Muscular Atrophy, medicine.anatomical_structure, Neurology, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Adult, Genetic Markers, medicine.medical_specialty, Adolescent, Biology, MESH: Deltoid Muscle, 03 medical and health sciences, MESH: Gene Expression Profiling, Atrophy, Deltoid muscle, medicine, Humans, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, Gene Expression Profiling, Amyotrophic Lateral Sclerosis, MESH: Muscular Atrophy, Skeletal muscle, MESH: Adult, medicine.disease, MESH: Male, Gene Expression Regulation, Case-Control Studies, Neurology (clinical), MESH: Female, 030217 neurology & neurosurgery
Abstract: Background: Amyotrophic lateral sclerosis (ALS) is a fatal adult-onset degenerative disease characterized by the loss of upper and lower motor neurons leading to progressive muscle atrophy and paralysis. The lack of molecular markers of the progression of disease is detrimental to clinical practice and therapeutic trials. Objective: This study was designed to identify gene expression changes in skeletal muscle that could reliably define the degree of disease severity. Methods: Gene expression profiles were obtained from the deltoid muscles of ALS patients and healthy subjects. Changes in differentially expressed genes were compared to the status of deltoid muscle disability, as determined by manual muscle testing, electrophysiology and the degree of myofiber atrophy. Functionally related genes were grouped by annotation analysis, and deltoid muscle injury was predicted using binary tree classifiers. Results: Two sets of 25 and 70 transcripts appeared differentially regulated exclusively in early and advanced states of deltoid muscle impairment, respectively. The expression of another set of 198 transcripts correlated with a composite score of muscle injury combining manual muscle testing and histological examination. From the totality of these expression changes, 155 transcripts distinguished advanced from early deltoid muscle impairment with 80% sensitivity and 100% specificity. Nine of these transcripts, known also to be regulated in ALS mouse and surgically denervated muscle, predicted the advanced disease status with 100% sensitivity and specificity. Conclusion: We provide robust gene expression changes that can be of practical use when monitoring ALS status and the effects of disease-modifying drugs.
Published: 2012

19. G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

Author: Claudia Pitzer, Armin Schneider, Alexandre Henriques, Luc Dupuis, SYGNIS Bioscience, Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), and BMC, Ed.
Subjects: medicine.medical_treatment, Apoptosis, Cell Count, MESH: Animals, Newborn, MESH: Spinal Cord, Mice, MESH: Lumbar Vertebrae, 0302 clinical medicine, Granulocyte Colony-Stimulating Factor, MESH: Animals, MESH: Cell Size, Motor Neurons, MESH: Choline O-Acetyltransferase, 0303 health sciences, Lumbar Vertebrae, General Neuroscience, lcsh:QP351-495, Brain, Axotomy, Sciatic Nerve, Granulocyte colony-stimulating factor, Cell biology, MESH: Sciatic Nerve, medicine.anatomical_structure, Spinal Cord, MESH: Cell Survival, Receptors, Granulocyte Colony-Stimulating Factor, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Sciatic nerve, MESH: Motor Neurons, Research Article, Genetically modified mouse, MESH: Axons, Cell Survival, MESH: Mice, Transgenic, SOD1, Central nervous system, Mice, Transgenic, MESH: Axotomy, Biology, Neuroprotection, lcsh:RC321-571, Choline O-Acetyltransferase, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Brain, MESH: Receptors, Granulocyte Colony-Stimulating Factor, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, MESH: Mice, 030304 developmental biology, Cell Size, MESH: Cell Count, Growth factor, MESH: Apoptosis, Axons, Disease Models, Animal, lcsh:Neurophysiology and neuropsychology, Animals, Newborn, nervous system, MESH: Granulocyte Colony-Stimulating Factor, MESH: Disease Models, Animal, Neuroscience, 030217 neurology & neurosurgery
Abstract: Background Granulocyte colony stimulating factor (G-CSF) is a growth factor essential for generation of neutrophilic granulocytes. Apart from this hematopoietic function, we have recently uncovered potent neuroprotective and regenerative properties of G-CSF in the central nervous system (CNS). The G-CSF receptor and G-CSF itself are expressed in α motoneurons, G-CSF protects motoneurons, and improves outcome in the SOD1(G93A) transgenic mouse model for amyotrophic lateral sclerosis (ALS). In vitro, G-CSF acts anti-apoptotically on motoneuronal cells. Due to the pleiotrophic effects of G-CSF and the complexity of the SOD1 transgenic ALS models it was however not possible to clearly distinguish between directly mediated anti-apoptotic and indirectly protective effects on motoneurons. Here we studied whether G-CSF is able to protect motoneurons from purely apoptotic cell death induced by a monocausal paradigm, neonatal sciatic nerve axotomy. Results We performed sciatic nerve axotomy in neonatal mice overexpressing G-CSF in the CNS and found that G-CSF transgenic mice displayed significantly higher numbers of surviving lumbar motoneurons 4 days following axotomy than their littermate controls. Also, surviving motoneurons in G-CSF overexpressing animals were larger, suggesting additional trophic effects of this growth factor. Conclusions In this model of pure apoptotic cell death the protective effects of G-CSF indicate direct actions of G-CSF on motoneurons in vivo. This shows that G-CSF exerts potent anti-apoptotic activities towards motoneurons in vivo and suggests that the protection offered by G-CSF in ALS mouse models is due to its direct neuroprotective activity.
Published: 2010

20. Platelet serotonin level predicts survival in amyotrophic lateral sclerosis

Author: François Salachas, Gilbert Bensimon, Jean-Philippe Loeffler, Philippe Jullien, Luc Dupuis, Lucette Lacomblez, Odile Spreux-Varoquaux, Gaëlle Bruneteau, Vincent Meininger, Pierre-François Pradat, Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Biologie [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de pharmacologie médicale [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Fédération des Maladies du Système Nerveux, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Fonctionnelle (LIF), Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-IFR49-Institut National de la Santé et de la Recherche Médicale (INSERM), Dr. Dupuis received research support from the Amyotrophic Lateral Sclerosis Association (Grant 1698, ALSA). Drs. Dupuis, Lacomblez, Pradat and Pr Meininger received support from the association pour la recherche sur la sclerose laterale amyotrophique (ARSla). Drs. Loeffler, Lacomblez and Pradat received research support from the Association Francaise contre les Myopathies (AFM). Pr Meininger received research support from Teva Pharma, GSK and Trophos. Dr. Lacomblez received research support from Trophos, Eisai, GSK, Novartis and Janssen-Cilag., Service de Pharmacologie médicale [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Dupuis, Luc, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Blood Platelets, Serotonin, medicine.medical_specialty, Pathology, Science, Neurological Disorders/Neuromuscular Diseases, Disease, Biology, Serotonergic, Neurological Disorders, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Blood plasma, medicine, Humans, Platelet, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amyotrophic lateral sclerosis, Chromatography, High Pressure Liquid, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Proportional hazards model, Amyotrophic Lateral Sclerosis, Hydroxyindoleacetic Acid, Motor neuron, medicine.disease, Survival Analysis, 3. Good health, Endocrinology, medicine.anatomical_structure, Case-Control Studies, Medicine, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuroscience/Neurobiology of Disease and Regeneration, 030217 neurology & neurosurgery, Research Article, Neuroscience
Abstract: BackgroundAmyotrophic lateral sclerosis (ALS) is a life-threatening neurodegenerative disease involving upper and lower motor neurons loss. Clinical features are highly variable among patients and there are currently few known disease-modifying factors underlying this heterogeneity. Serotonin is involved in a range of functions altered in ALS, including motor neuron excitability and energy metabolism. However, whether serotoninergic activity represents a disease modifier of ALS natural history remains unknown.MethodologyPlatelet and plasma unconjugated concentrations of serotonin and plasma 5-HIAA, the major serotonin metabolite, levels were measured using HPLC with coulometric detection in a cohort of 85 patients with ALS all followed-up until death and compared to a control group of 29 subjects.Principal findingsPlatelet serotonin levels were significantly decreased in ALS patients. Platelet serotonin levels did not correlate with disease duration but were positively correlated with survival of the patients. Univariate Cox model analysis showed a 57% decreased risk of death for patients with platelet serotonin levels in the normal range relative to patients with abnormally low platelet serotonin (p = 0.0195). This protective effect remained significant after adjustment with age, gender or site of onset in multivariate analysis. Plasma unconjugated serotonin and 5-HIAA levels were unchanged in ALS patients compared to controls and did not correlate with clinical parameters.Conclusions/significanceThe positive correlation between platelet serotonin levels and survival strongly suggests that serotonin influences the course of ALS disease.
Published: 2010

21. [Amyotrophic lateral sclerosis: role of energy deficiency in neuromuscular junction dismantlement.]

Author: Luc Dupuis, Jean-Philippe Loeffler, Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), and Dupuis, Luc
Subjects: Motor Neurons, Muscle Cells, Superoxide Dismutase, Macrophages, Nogo Proteins, Amyotrophic Lateral Sclerosis, Models, Neurological, Neuromuscular Junction, Muscle Proteins, Mice, Transgenic, Nerve Tissue Proteins, Disease Models, Animal, Mice, Phenotype, Superoxide Dismutase-1, Species Specificity, Astrocytes, Animals, Humans, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Energy Metabolism, Myelin Proteins
Abstract: International audience; Amyotrophic lateral sclerosis (ALS) is the most frequent adult onset motor neuron disorder. A subset of ALS cases is linked to mutations in the copper/zinc superoxide dismutase (sod1) gene and detailed phenotypic analysis of transgenic mice overexpressing mutant forms of SOD1 (mSOD1) allowed a better understanding of the pathophysiological mechanisms leading to motor neuron death. The promising results obtained in these animal models however poorly translated into conclusive clinical trials. In this review, we summarize the main pathological mechanisms at work in mSOD1 mice. In particular, recent results showed that the key pathological event was the destruction of the neuromuscular junction rather than motor neuron death. Neuromuscular junction dismantlement is likely the result of a chronic energy deficiency at the level of the whole organism. These results, along with a comparative analysis between the phenotype of mSOD1 mice and ALS patients, suggest new therapeutic strategies and show the interests but also the limits of the animal models. double dagger.
Published: 2008

22. Role of skeletal muscle in Amyotrophic Lateral Sclerosis

Author: Picchiarelli, Gina, STAR, ABES, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, Jean-Philippe Loeffler, and Luc Dupuis
Subjects: Acetylcholine receptors, Jonction neuromusculaire, Récepteurs de l’acétylcholine, Neuromuscular junction, Muscle, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amyotrophic lateral sclerosis, FUS
Abstract: Amyotrophic lateral sclerosis is a neurodegenerative whose first symptoms generally appear around age 60. It is characterized by progressive motor neuron degeneration, paralysis and leading to death due to respiratory failure in a few years. Currently, there is no cure so the understanding of ALS physiopathology is necessary. Although many alterations in the muscle have been highlighted, its contribution in ALS remains to be defined. We showed that FUS is enriched in subsynaptic nuclei and this enrichment depended on innervation. Besides, FUS binds directly acetylcholine receptors (AchR) promoter and is required for Ermdependent induction of AChR expression. Conversely, mutant FUS is enriched on extra-synaptic nuclei and induce muscle intrinsic toxicity responsible for neuromuscular junction (NMJ) alteration. Beyond NMJ, FUS is required for muscle mitochondrial function and muscle differentiation through PRMT1-dependent MEF2A activation. Thus, FUS muscular toxicity plays a key role in the ALS physiopathology., La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative dont les premiers symptômes apparaissent généralement vers 60 ans. Elle affecte sélectivement le système moteur et provoque une paralysie progressive amenant au décès du patient par défaillance respiratoire en quelques années. À ce jour, il n’existe aucun traitement curatif, d’où la nécessité de comprendre la physiopathologie de la SLA. Bien que de nombreuses altérations dans le muscle aient été mises en évidence, sa contribution dans la SLA reste à définir. Nous avons montré que FUS est enrichi dans les noyaux sous-synaptiques de façon dépendante de l’innervation. De plus, FUS se lie au promoteur des récepteurs de l’acétylcholine et induit leur transcription de façon dépendante d’ERM. Le mutant FUS, quant à lui, est enrichi dans les noyaux extra-synaptiques et entraîne une toxicité musculaire responsable de l’altération de la jonction neuromusculaire (JNM). Au-delà de la JNM, FUS active MEF2A, de façon dépendante de PRMT1 afin de réguler les fonctions mitochondriales et la différenciation musculaire. La toxicité musculaire de FUS joue donc un rôle clé dans la physiopathologie de la SLA.
Published: 2018

23. Role of skeletal muscle in Amyotrophic Lateral Sclerosis

Author: Picchiarelli, Gina, STAR, ABES, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, Jean-Philippe Loeffler, and Luc Dupuis
Subjects: Acetylcholine receptors, Jonction neuromusculaire, Récepteurs de l’acétylcholine, Neuromuscular junction, Muscle, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Amyotrophic lateral sclerosis, FUS
Abstract: Amyotrophic lateral sclerosis is a neurodegenerative whose first symptoms generally appear around age 60. It is characterized by progressive motor neuron degeneration, paralysis and leading to death due to respiratory failure in a few years. Currently, there is no cure so the understanding of ALS physiopathology is necessary. Although many alterations in the muscle have been highlighted, its contribution in ALS remains to be defined. We showed that FUS is enriched in subsynaptic nuclei and this enrichment depended on innervation. Besides, FUS binds directly acetylcholine receptors (AchR) promoter and is required for Ermdependent induction of AChR expression. Conversely, mutant FUS is enriched on extra-synaptic nuclei and induce muscle intrinsic toxicity responsible for neuromuscular junction (NMJ) alteration. Beyond NMJ, FUS is required for muscle mitochondrial function and muscle differentiation through PRMT1-dependent MEF2A activation. Thus, FUS muscular toxicity plays a key role in the ALS physiopathology., La sclérose latérale amyotrophique (SLA) est une maladie neurodégénérative dont les premiers symptômes apparaissent généralement vers 60 ans. Elle affecte sélectivement le système moteur et provoque une paralysie progressive amenant au décès du patient par défaillance respiratoire en quelques années. À ce jour, il n’existe aucun traitement curatif, d’où la nécessité de comprendre la physiopathologie de la SLA. Bien que de nombreuses altérations dans le muscle aient été mises en évidence, sa contribution dans la SLA reste à définir. Nous avons montré que FUS est enrichi dans les noyaux sous-synaptiques de façon dépendante de l’innervation. De plus, FUS se lie au promoteur des récepteurs de l’acétylcholine et induit leur transcription de façon dépendante d’ERM. Le mutant FUS, quant à lui, est enrichi dans les noyaux extra-synaptiques et entraîne une toxicité musculaire responsable de l’altération de la jonction neuromusculaire (JNM). Au-delà de la JNM, FUS active MEF2A, de façon dépendante de PRMT1 afin de réguler les fonctions mitochondriales et la différenciation musculaire. La toxicité musculaire de FUS joue donc un rôle clé dans la physiopathologie de la SLA.
Published: 2018

24. Altérations hypothalamiques dans la sclérose latérale amyotrophique

Author: Vercruysse, Pauline, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, Luc Dupuis, Anke Witting, and STAR, ABES
Subjects: [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Comportement alimentaire, Melanocortin system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Amyotrophic Lateral Sclerosis, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Hypothalamus, Mélanocortine, Food intake behaviour, Sclérose Latérale Amyotrophique
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a major neurodegenerative disease characterised by a loss of upper and lower motor neurons. The loss of motor neurons leads to muscle atrophy and paralysis. Besides motor loss, weight loss is important in ALS patients. This symptom appears before first muscular symptoms and is correlated with survival. This defect of energetic metabolism is partially due to hypermetabolism associated with food intake problems. Hypothalamus is the part of brain controlling the energetic metabolism. The aim of my Ph.D. was to characterise hypothalamic alterations in ALS. First, we have shown a default in the melanocortin system of hypothalamus, and shown that this melanocortin defect correlates with alterations in food intake behaviour. Second, we demonstrated the existence of hypothalamic atrophy in ALS patients in the posterior part of the hypothalamus, including the lateral hypothalamic area (LHA). This atrophy was correlated with weight loss. Finally, we observed that hypothalamic MCH neurons, located in the LHA, are affected in ALS, and that MCH complementation rescues weight loss in a mouse model of ALS., La Sclérose Latérale Amyotrophique (SLA) est une maladie neurodégénérative due à la dégénérescence des motoneurones supérieurs et inférieurs. La perte des neurones moteurs entraine une atrophie puis une paralysie progressive des muscles. En plus de la perte musculaire, une perte de poids est importante chez les patients SLA. Ce symptôme apparaît avant les premiers symptômes moteurs et est corrélé avec la survie. Ce défaut du métabolisme énergétique est en partie dû à un hypermétabolisme associé à des problèmes de prise alimentaire. L’hypothalamus est la partie du cerveau contrôlant l’ensemble du métabolisme énergétique. L’objectif de ma thèse a été de caractériser les altérations hypothalamiques dans la SLA. Nous avons tout d’abord mis en évidence une anomalie du système mélanocortine de l’hypothalamus, et montré que cette anomalie était associée à des modifications du comportement alimentaire. Ensuite, nos travaux ont mis en évidence une atrophie de la partie postérieure de l’hypothalamus, comprenant l’aire hypothalamique latérale (LHA), des patients SLA, corrélée à la perte de poids. Finalement, nous démontré que les neurones produisant le MCH, situés dans le LHA, sont atteints dans la SLA et qu’une complémentation en MCH empêche la perte de poids dans un modèle animal de SLA.
Published: 2016

25. The role of serotoninergic neurons in amyotrophic lateral sclerosis

Author: El Oussini-Ben Chaabane , Hajer, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, Luc Dupuis, STAR, ABES, and Université de Strasbourg ( UNISTRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Serotoninergic neurons, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, fungi, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Sclérose amyotrophique latérale, Spasticité, Amyotrophic lateral sclerosis, nervous system, Neuroinflammation, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Serotonin receptor 5-HT2B, Spasticity, Neurones sérotoninergiques, Récepteur 2B de la sérotonine
Abstract: Amyotrophic lateral sclerosis (SLA) is a neurodegenerative disease characterize by the loss of upper motor neurons in the motor cortex and lower motor neurons in the brainstem and spinal cord. The loss of motor neurons leads to muscle atrophy and progressive paralysis. In 2013 our laboratory identified a new neuronal population affected in ALS. They observed the degeneration of serotoninergic neurons in ALS patients and animal models. For this, the aim of my PhD is to identify the role of serotoninergic neurons in case of ALS. We observed an upregulation of serotonin receptor 5-HT2B in ALS mice models. The investigation of the role of 5-HT2B receptor in case of ALS showed its role as a disease modulator. The loss of 5-HT2B receptor accelerated disease progression and modulated neuroinflammatory response. Moreover, our results showed that the loss of serotoninergic neurons is responsible of the development of spasticity, a painful symptom observed in ALS patients. All these opened the way for therapeutic strategies targeting spasticity and neuroinflammation in case of ALS., La sclérose amyotrophique latérale (SLA) est une maladie neurodégénérative due à la dégénérescence des motoneurones supérieurs dans le cortex moteur et des motoneurones inférieurs situés dans la moelle épinière et le tronc cérébral. La perte des neurones moteurs provoque l’atrophie et la paralysie progressive des muscles. Notre laboratoire a démontré en 2013 que la dégénérescence associée à la SLA n’était pas limitée aux motoneurones mais aussi aux neurones sérotoninergiques chez les patients et les modèles animaux de SLA. L’objectif de ma thèse a été de caractériser le rôle des neurones sérotoninergiques dans la SLA. On a observé une augmentation de l’expression du gène codant pour le récepteur 2B de la sérotonine (5-HT2B) chez les modèles murins de SLA. L’analyse du rôle du récepteur 5-HT2B dans le cas de SLA a montré que ce dernier est un modulateur de la maladie. La perte du récepteur 5-HT2B accélère la progression de la maladie et modifie la régulation de la réponse inflammatoire. En plus, nos travaux ont révélé que la perte des neurones sérotoninergiques est à l’origine du développement de la spasticité, un symptôme douloureux chez les patients SLA. Ces résultats ouvrent la voie à des approches thérapeutiques qui ciblent cette population neuronale affectée lors de la maladie pour traiter la spasticité et la neuroinflammation au cours de la maladie.
Published: 2016

26. Conditional truncation of the FUS protein in mice : a new animal model of the ALS/FTD continuum

Author: Scekic-Zahirovic, Jelena, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, Universität Basel, Université de Fribourg (Fribourg, Suisse), Luc Dupuis, Marlene Bartos, Pico Caroni, and STAR, ABES
Subjects: Cytoplasmic mislocalization, SLA/DFT, Cytoplasmique localisation, ALS/FTLD, Toxic gain of function, Gain de fonction, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], FUS
Abstract: Amyotrophic lateral sclerosis (ALS) and Frontotemporal dementia (FTLD) are now considered as a unique clinicopathological spectrum referred to as ALS/FTLD. Cytoplasmic aggregation of the physiologically nuclear FUS protein is a hallmark feature of a subset of ALS/FTLD. It remains unknonwn whether the critical pathogenic event relies on a loss of FUS normal nuclear functions, a toxic gain of function of FUS in the cytoplasm, or a combination of both.To answer this question we have generated a conditional mouse model expressing truncated FUS without nuclear localization signal - FusΔNLS. Our data showed that complete cytoplasmic mislocalization of truncated FUS protein within spinal motor neurons is a major determinant of motor neuron degeneration via toxic gain of function. A partial mislocalization of truncated FUS protein was sufficient to trigger key features of ALS and of FTLD.These studies allowed the elucidation of mechanisms underlying FUS role in ALS/FTLD, and will hopefully lead to development of therapies for these devastating diseases., La sclérose latérale amyotrophique (SLA) et la démence fronto-temporale (DFT) sont deux maladies qui constituent un continuum clinico-pathologique. La mutation de FUS, une protéine nucléaire à fonctions multiples, provoque des cas familaux de SLA, et ces mutations provoquent une redistribution sub-cellulaire de FUS, du noyau vers le cytoplasme. Certains cas de DFT présentent une telles distribution anormale en l’absence de mutations de FUS. Il n’est pas connu si la maladie est provoquée par une perte de la fonction nucléaire de FUS et/ou un gain de fonction cytoplasmique.Nous avons généré et caractérisé une lignée de souris exprimant une forme cytoplasmique de FUS (Fus-ΔNLS). La localisation exclusive de FUS dans le cytoplasme provoque la mort des motoneurones via un gain de fonction dans les motoneurones eux-mêmes. Une localisation cytoplasmique partielle de FUS est suffisante pour développer un phénotype de la SLA et de DFT. Les mécanismes élucidés permettront de comprendre les bases des SLA/DFT.
Published: 2016

27. Rôle des neurones sérotoninergiques dans la sclérose latérale amyotrophique

Author: El Oussini-Ben Chaabane, Hajer, STAR, ABES, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, and Luc Dupuis
Subjects: nervous system, Neuroinflammation, Serotoninergic neurons, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, fungi, Serotonin receptor 5-HT2B, Sclérose amyotrophique latérale, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Spasticity, Neurones sérotoninergiques, Spasticité, Récepteur 2B de la sérotonine, Amyotrophic lateral sclerosis
Abstract: Amyotrophic lateral sclerosis (SLA) is a neurodegenerative disease characterize by the loss of upper motor neurons in the motor cortex and lower motor neurons in the brainstem and spinal cord. The loss of motor neurons leads to muscle atrophy and progressive paralysis. In 2013 our laboratory identified a new neuronal population affected in ALS. They observed the degeneration of serotoninergic neurons in ALS patients and animal models. For this, the aim of my PhD is to identify the role of serotoninergic neurons in case of ALS. We observed an upregulation of serotonin receptor 5-HT2B in ALS mice models. The investigation of the role of 5-HT2B receptor in case of ALS showed its role as a disease modulator. The loss of 5-HT2B receptor accelerated disease progression and modulated neuroinflammatory response. Moreover, our results showed that the loss of serotoninergic neurons is responsible of the development of spasticity, a painful symptom observed in ALS patients. All these opened the way for therapeutic strategies targeting spasticity and neuroinflammation in case of ALS., La sclérose amyotrophique latérale (SLA) est une maladie neurodégénérative due à la dégénérescence des motoneurones supérieurs dans le cortex moteur et des motoneurones inférieurs situés dans la moelle épinière et le tronc cérébral. La perte des neurones moteurs provoque l’atrophie et la paralysie progressive des muscles. Notre laboratoire a démontré en 2013 que la dégénérescence associée à la SLA n’était pas limitée aux motoneurones mais aussi aux neurones sérotoninergiques chez les patients et les modèles animaux de SLA. L’objectif de ma thèse a été de caractériser le rôle des neurones sérotoninergiques dans la SLA. On a observé une augmentation de l’expression du gène codant pour le récepteur 2B de la sérotonine (5-HT2B) chez les modèles murins de SLA. L’analyse du rôle du récepteur 5-HT2B dans le cas de SLA a montré que ce dernier est un modulateur de la maladie. La perte du récepteur 5-HT2B accélère la progression de la maladie et modifie la régulation de la réponse inflammatoire. En plus, nos travaux ont révélé que la perte des neurones sérotoninergiques est à l’origine du développement de la spasticité, un symptôme douloureux chez les patients SLA. Ces résultats ouvrent la voie à des approches thérapeutiques qui ciblent cette population neuronale affectée lors de la maladie pour traiter la spasticité et la neuroinflammation au cours de la maladie.
Published: 2016

28. Altérations hypothalamiques dans la sclérose latérale amyotrophique

Author: Vercruysse, Pauline, STAR, ABES, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg, Luc Dupuis, and Anke Witting
Subjects: Comportement alimentaire, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Melanocortin system, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Amyotrophic Lateral Sclerosis, Mélanocortine, Hypothalamus, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Food intake behaviour, Sclérose Latérale Amyotrophique
Abstract: Amyotrophic Lateral Sclerosis (ALS) is a major neurodegenerative disease characterised by a loss of upper and lower motor neurons. The loss of motor neurons leads to muscle atrophy and paralysis. Besides motor loss, weight loss is important in ALS patients. This symptom appears before first muscular symptoms and is correlated with survival. This defect of energetic metabolism is partially due to hypermetabolism associated with food intake problems. Hypothalamus is the part of brain controlling the energetic metabolism. The aim of my Ph.D. was to characterise hypothalamic alterations in ALS. First, we have shown a default in the melanocortin system of hypothalamus, and shown that this melanocortin defect correlates with alterations in food intake behaviour. Second, we demonstrated the existence of hypothalamic atrophy in ALS patients in the posterior part of the hypothalamus, including the lateral hypothalamic area (LHA). This atrophy was correlated with weight loss. Finally, we observed that hypothalamic MCH neurons, located in the LHA, are affected in ALS, and that MCH complementation rescues weight loss in a mouse model of ALS., La Sclérose Latérale Amyotrophique (SLA) est une maladie neurodégénérative due à la dégénérescence des motoneurones supérieurs et inférieurs. La perte des neurones moteurs entraine une atrophie puis une paralysie progressive des muscles. En plus de la perte musculaire, une perte de poids est importante chez les patients SLA. Ce symptôme apparaît avant les premiers symptômes moteurs et est corrélé avec la survie. Ce défaut du métabolisme énergétique est en partie dû à un hypermétabolisme associé à des problèmes de prise alimentaire. L’hypothalamus est la partie du cerveau contrôlant l’ensemble du métabolisme énergétique. L’objectif de ma thèse a été de caractériser les altérations hypothalamiques dans la SLA. Nous avons tout d’abord mis en évidence une anomalie du système mélanocortine de l’hypothalamus, et montré que cette anomalie était associée à des modifications du comportement alimentaire. Ensuite, nos travaux ont mis en évidence une atrophie de la partie postérieure de l’hypothalamus, comprenant l’aire hypothalamique latérale (LHA), des patients SLA, corrélée à la perte de poids. Finalement, nous démontré que les neurones produisant le MCH, situés dans le LHA, sont atteints dans la SLA et qu’une complémentation en MCH empêche la perte de poids dans un modèle animal de SLA.
Published: 2016

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28 results on '"Luc Dupuis"'

1. Atxn2-CAG100-KnockIn mouse spinal cord shows progressive TDP43 pathology associated with cholesterol biosynthesis suppression

2. Dysregulation of energy homeostasis in amyotrophic lateral sclerosis

3. Linking neuroinflammation to motor neuron degeneration in ALS: The critical role of CXCL13/CXCR5

4. Effect of high-caloric nutrition on serum neurofilament light chain levels in amyotrophic lateral sclerosis

5. Association of Insulin-like Growth Factor 1 Concentrations with Risk for and Prognosis of Amyotrophic Lateral Sclerosis - Results from the ALS Registry Swabia

6. Effect of High‐Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis

7. FUS-mediated regulation of acetylcholine receptor transcription at neuromuscular junctions is compromised in amyotrophic lateral sclerosis

8. Paradox of amyotrophic lateral sclerosis and energy metabolism

9. The VAMP‐associated protein VAPB is required for cardiac and neuronal pacemaker channel function

10. Association of Serum Retinol-Binding Protein 4 Concentration With Risk for and Prognosis of Amyotrophic Lateral Sclerosis

11. Thermoregulation in amyotrophic lateral sclerosis

12. Hypertonic Stress Causes Cytoplasmic Translocation of Neuronal, but Not Astrocytic, FUS due to Impaired Transportin Function

13. Adipokines, C-reactive protein and Amyotrophic Lateral Sclerosis – results from a population- based ALS registry in Germany

14. Life course body mass index and risk and prognosis of amyotrophic lateral sclerosis: results from the ALS registry Swabia

15. ALS-causing mutations differentially affect PGC-1α expression and function in the brain vs. peripheral tissues

16. Body fat distribution in Parkinson's disease: An MRI-based body fat quantification study

17. Erratum

18. Muscle gene expression is a marker of amyotrophic lateral sclerosis severity

19. G-CSF protects motoneurons against axotomy-induced apoptotic death in neonatal mice

20. Platelet serotonin level predicts survival in amyotrophic lateral sclerosis

21. [Amyotrophic lateral sclerosis: role of energy deficiency in neuromuscular junction dismantlement.]

22. Role of skeletal muscle in Amyotrophic Lateral Sclerosis

23. Role of skeletal muscle in Amyotrophic Lateral Sclerosis

24. Altérations hypothalamiques dans la sclérose latérale amyotrophique

25. The role of serotoninergic neurons in amyotrophic lateral sclerosis

26. Conditional truncation of the FUS protein in mice : a new animal model of the ALS/FTD continuum

27. Rôle des neurones sérotoninergiques dans la sclérose latérale amyotrophique

28. Altérations hypothalamiques dans la sclérose latérale amyotrophique

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