Search

Your search keyword '"Olivia Massiani-Beaudoin"' showing total 5 results
Start Over Author "Olivia Massiani-Beaudoin"
5 results on '"Olivia Massiani-Beaudoin"'

1. Retrotransposons as a Source of DNA Damage in Neurodegeneration

Author

Eugenie Peze-Heidsieck, Tom Bonnifet, Rania Znaidi, Camille Ravel-Godreuil, Olivia Massiani-Beaudoin, Rajiv L. Joshi, and Julia Fuchs

Subjects
transposable elements (TEs), genomic instability, LINE-1, DNA damage, neurodegenerative diseases, Parkinson’s disease, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The etiology of aging-associated neurodegenerative diseases (NDs), such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), still remains elusive and no curative treatment is available. Age is the major risk factor for PD and AD, but the molecular link between aging and neurodegeneration is not fully understood. Aging is defined by several hallmarks, some of which partially overlap with pathways implicated in NDs. Recent evidence suggests that aging-associated epigenetic alterations can lead to the derepression of the LINE-1 (Long Interspersed Element-1) family of transposable elements (TEs) and that this derepression might have important implications in the pathogenesis of NDs. Almost half of the human DNA is composed of repetitive sequences derived from TEs and TE mobility participated in shaping the mammalian genomes during evolution. Although most TEs are mutated and no longer mobile, more than 100 LINE-1 elements have retained their full coding potential in humans and are thus retrotransposition competent. Uncontrolled activation of TEs has now been reported in various models of neurodegeneration and in diseased human brain tissues. We will discuss in this review the potential contribution of LINE-1 elements in inducing DNA damage and genomic instability, which are emerging pathological features in NDs. TEs might represent an important molecular link between aging and neurodegeneration, and a potential target for urgently needed novel therapeutic disease-modifying interventions.

Published
2022
Full Text
View/download PDF

2. Perturbed DNA methylation by Gadd45b induces chromatin disorganization, DNA strand breaks and dopaminergic neuron death

Author

Camille Ravel-Godreuil, Olivia Massiani-Beaudoin, Philippe Mailly, Alain Prochiantz, Rajiv L. Joshi, and Julia Fuchs

Subjects
molecular biology, epigenetics, molecular neuroscience, Science
Abstract

Summary: Age is a major risk factor for neurodegenerative diseases like Parkinson’s disease, but few studies have explored the contribution of key hallmarks of aging, namely DNA methylation changes and heterochromatin destructuration, in the neurodegenerative process. Here, we investigated the consequences of viral overexpression of Gadd45b, a multifactorial protein involved in DNA demethylation, in the mouse midbrain. Gadd45b overexpression induced global and stable changes in DNA methylation, particularly in introns of genes related to neuronal functions, as well as on LINE-1 transposable elements. This was paralleled by disorganized heterochromatin, increased DNA damage, and vulnerability to oxidative stress. LINE-1 de-repression, a potential source of DNA damage, preceded Gadd45b-induced neurodegeneration, whereas prolonged Gadd45b expression deregulated expression of genes related to heterochromatin maintenance, DNA methylation, or Parkinson’s disease. Our data indicates that aging-related alterations contribute to dopaminergic neuron degeneration with potential implications for Parkinson’s disease.

Published
2021
Full Text
View/download PDF

3. Engrailed Homeoprotein Protects Mesencephalic Dopaminergic Neurons from Oxidative Stress

Author

Hocine Rekaik, François-Xavier Blaudin de Thé, Julia Fuchs, Olivia Massiani-Beaudoin, Alain Prochiantz, and Rajiv L. Joshi

Subjects
Biology (General), QH301-705.5
Abstract

Engrailed homeoproteins are expressed in adult dopaminergic neurons of the substantia nigra. In Engrailed1 heterozygous mice, these neurons start dying at 6 weeks, are more sensitive to oxidative stress, and progressively develop traits similar to those observed following an acute and strong oxidative stress inflected to wild-type neurons. These changes include DNA strand breaks and the modification (intensity and distribution) of several nuclear and nucleolar heterochromatin marks. Engrailed1 and Engrailed2 are biochemically equivalent transducing proteins previously used to antagonize dopaminergic neuron death in Engrailed1 heterozygous mice and in mouse models of Parkinson disease. Accordingly, we show that, following an acute oxidative stress, a single Engrailed2 injection restores all nuclear and nucleolar heterochromatin marks, decreases the number of DNA strand breaks, and protects dopaminergic neurons against apoptosis.

Published
2015
Full Text
View/download PDF

4. Perturbed DNA Methylation by Sustained Overexpression of Gadd45b Induces Chromatin Disorganization, DNA Strand Breaks and Dopaminergic Neuron Death in Mice

Author

Olivia Massiani-Beaudoin, Rajiv L. Joshi, Philippe Mailly, Julia Fuchs, Camille Ravel-Godreuil, Alain Prochiantz, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Collège de France (CdF (institution))

Subjects
0303 health sciences, 050208 finance, Heterochromatin, DNA damage, [SCCO.NEUR]Cognitive science/Neuroscience, Neurodegeneration, 05 social sciences, Biology, medicine.disease, Chromatin, Cell biology, 03 medical and health sciences, 0302 clinical medicine, DNA demethylation, DNA methylation, 0502 economics and business, medicine, Heterochromatin maintenance, Heterochromatin organization, 050207 economics, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Heterochromatin disorganization is a key hallmark of aging and DNA methylation state is currently the main molecular predictor of chronological age. The most frequent neurodegenerative diseases like Parkinson disease and Alzheimer’s disease are age-related but how the aging process and chromatin alterations are linked to neurodegeneration is unknown. Here, we investigated the consequences of viral overexpression of Gadd45b, a multifactorial protein involved in active DNA demethylation, in the midbrain of wild-type mice. Gadd45b overexpression induces global and stable changes in DNA methylation, particularly on gene bodies of genes related to neuronal functions. DNA methylation changes were accompanied by perturbed H3K9me3-marked heterochromatin and increased DNA damage. Prolonged Gadd45b expression resulted in dopaminergic neuron degeneration accompanied by altered expression of candidate genes related to heterochromatin maintenance, DNA methylation or Parkinson disease. Gadd45b overexpression rendered midbrain dopaminergic neurons more vulnerable to acute oxidative stress. Heterochromatin disorganization and DNA demethylation resulted in derepression of mostly young LINE-1 transposable elements, a potential source of DNA damage, prior to Gadd45b-induced neurodegeneration. Our data implicate that alterations in DNA methylation and heterochromatin organization, LINE-1 derepression and DNA damage can represent important contributors in the pathogenic mechanisms of dopaminergic neuron degeneration with potential implications for Parkinson disease.

Published
2021

5. Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial complex I insults

Author

François Castagner, Olivia Massiani-Beaudoin, Alain Prochiantz, Andreas Hartmann, Wolfgang H. Oertel, Julia Fuchs, Kenneth L. Moya, Olivier Stettler, Rajiv L. Joshi, Anne Lombès, Wolfgang Faigle, Colette Bouillot, Daniel Alvarez-Fischer, Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris sciences et lettres (PSL), Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS), Collège de France (CDF (laboratoire)), Collège de France (CdF (institution)), Somnomar, Sleep Research Institute, 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), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-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), Collège de France - Chaire Processus morphogénétiques, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Peer, Hal, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Chaire Processus morphogénétiques, Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, and Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, [SDV]Life Sciences [q-bio], Dopamine, Cell Count, chemistry.chemical_compound, Mice, 0302 clinical medicine, Mesencephalon, RNA, Small Interfering, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, Chromatography, High Pressure Liquid, Neurons, 0303 health sciences, NDUFS1, General Neuroscience, MPTP, Dopaminergic, Neurodegeneration, Nitro Compounds, alpha-Synuclein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Signal Transduction, Tyrosine 3-Monooxygenase, Neurotoxins, Substantia nigra, Mice, Transgenic, Nerve Tissue Proteins, Biology, Development, In Vitro Techniques, Neurological Disorders, Midbrain, 03 medical and health sciences, Rotenone, medicine, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Oxidopamine, 030304 developmental biology, Homeodomain Proteins, Dopamine Plasma Membrane Transport Proteins, Pars compacta, NADH Dehydrogenase, medicine.disease, Embryo, Mammalian, engrailed, Mice, Inbred C57BL, chemistry, nervous system, Electron Transport Chain Complex Proteins, Dizocilpine Maleate, Propionates, Stereotyped Behavior, Neuroscience, 030217 neurology & neurosurgery
Abstract

Mice heterozygous for the homeobox gene Engrailed-1 (En1) display progressive loss of mesencephalic dopaminergic (mDA) neurons. We report that exogenous Engrailed-1 and Engrailed-2 (collectively Engrailed) protect mDA neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I toxin used to model Parkinson's disease in animals. Engrailed enhances the translation of nuclearly encoded mRNAs for two key complex I subunits, Ndufs1 and Ndufs3, and increases complex I activity. Accordingly, in vivo protection against MPTP by Engrailed is antagonized by Ndufs1 small interfering RNA. An association between Engrailed and complex I is further confirmed by the reduced expression of Ndufs1 and Ndufs3 in the substantia nigra pars compacta of En1 heterozygous mice. Engrailed also confers in vivo protection against 6-hydroxydopamine and α-synuclein-A30P. Finally, the unilateral infusion of Engrailed into the midbrain increases striatal dopamine content, resulting in contralateral amphetamine-induced turning. Therefore, Engrailed is both a survival factor for adult mDA neurons and a regulator of their physiological activity.

Published
2011

Catalog

Books, media, physical & digital resources
See catalog results