10 results on '"TEDESCHI, VALENTINA"'
Search Results
2. Additional file 4 of Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-l-alanine
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Petrozziello, Tiziana, Boscia, Francesca, Tedeschi, Valentina, Pannaccione, Anna, de Rosa, Valeria, Corvino, Angela, Severino, Beatrice, Annunziato, Lucio, and Secondo, Agnese
- Abstract
Additional file 3. Bar graph depicting the effect of L-BMAA (0.01-1 mM) on cell survival of differentiated NSC-34 cells. Data are expressed as mean��S.E. of three different experimental sessions. *p
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- 2022
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3. Additional file 2 of Na+/Ca2+ exchanger isoform 1 takes part to the Ca2+-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-l-alanine
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Petrozziello, Tiziana, Boscia, Francesca, Tedeschi, Valentina, Pannaccione, Anna, de Rosa, Valeria, Corvino, Angela, Severino, Beatrice, Annunziato, Lucio, and Secondo, Agnese
- Abstract
Additional file 1. (A) Immunolocalization of NCX1 (a,d) and MAP2 (b,e) within a motor-neuron enriched culture under control conditions. Nuclei were stained with nuclear DNA stain 4, 6-diamino-2-phenylinndole (DAPI). Arrows indicate MAP2-positive cells with higher level of NCX1 expression. (B) Immunolocalization of NCX1 and NCX3 in differentiated NSC-34 cells. (C) Quantification of SOD1-induced [Ca2+]i in presence of CNQX (20 ��M), MK801 (10 ��M), or CB-DMB (1 ��M) in motor neurons expressed as ���% of increase. All the experiments were repeated at least three times on at least 35 cells for each group; *p < 0.001 vs control (basal values of [Ca2+]i) .
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- 2022
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4. MOESM1 of The Ankylosing Spondylitis-Associated HLA-B*2705 Presents a B*0702-Restricted EBV Epitope and Sustains the Clonal Amplification of Cytotoxic T Cells in Patients
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Tedeschi, Valentina, Vitulano, Carolina, Cauli, Alberto, Paladini, Fabiana, Piga, Matteo, Mathieu, Alessandro, Sorrentino, Rosa, and Fiorillo, Maria
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The Ankylosing Spondylitis-Associated HLA-B*2705 Presents a B*0702-Restricted EBV Epitope and Sustains the Clonal Amplification of Cytotoxic T Cells in Patients
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- 2016
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5. HLA-B*2705 and its double implication in viral defense and autoimmunity: unpredicted presentation of an immunodominant viral epitope devoid of the classical B27 binding motif
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Tedeschi, Valentina, Vitulano, Carolina, Cauli, A, Mathieu, A, Paladini, Fabiana, Kormann, D, Bockmann, R, Sorrentino, Rosa, and Fiorillo, Maria Teresa
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- 2015
6. SARS-CoV-2 Spike Protein Activates Human Lung Macrophages
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Francesco Palestra, Remo Poto, Renato Ciardi, Giorgia Opromolla, Agnese Secondo, Valentina Tedeschi, Anne Lise Ferrara, Rosa Maria Di Crescenzo, Maria Rosaria Galdiero, Leonardo Cristinziano, Luca Modestino, Gianni Marone, Alfonso Fiorelli, Gilda Varricchi, Stefania Loffredo, Palestra, Francesco, Poto, Remo, Ciardi, Renato, Opromolla, Giorgia, Secondo, Agnese, Tedeschi, Valentina, Ferrara, Anne Lise, Di Crescenzo, Rosa Maria Di, Galdiero, Maria Rosaria, Cristinziano, Leonardo, Modestino, Luca, Marone, Gianni, Fiorelli, Alfonso, Varricchi, Gilda, and Loffredo, Stefania
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Organic Chemistry ,COVID-19 ,ACE2 ,General Medicine ,Keywords: COVID-19 ,spike protein ,Catalysis ,cytokines ,Computer Science Applications ,macrophages ,Inorganic Chemistry ,cytokine ,Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,TMPRSS2 - Abstract
COVID-19 is a viral disease caused by SARS-CoV-2. This disease is characterized primarily, but not exclusively, by respiratory tract inflammation. SARS-CoV-2 infection relies on the binding of spike protein to ACE2 on the host cells. The virus uses the protease TMPRSS2 as an entry activator. Human lung macrophages (HLMs) are the most abundant immune cells in the lung and fulfill a variety of specialized functions mediated by the production of cytokines and chemokines. The aim of this project was to investigate the effects of spike protein on HLM activation and the expression of ACE2 and TMPRSS2 in HLMs. Spike protein induced CXCL8, IL-6, TNF-α, and IL-1β release from HLMs; promoted efficient phagocytosis; and induced dysfunction of intracellular Ca2+ concentration by increasing lysosomal Ca2+ content in HLMs. Microscopy experiments revealed that HLM tracking was affected by spike protein activation. Finally, HLMs constitutively expressed mRNAs for ACE2 and TMPRSS2. In conclusion, during SARS-CoV-2 infection, macrophages seem to play a key role in lung injury, resulting in immunological dysfunction and respiratory disease.
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- 2023
7. Size-Based Effects of Anthropogenic Ultrafine Particles on Lysosomal TRPML1 Channel and Autophagy in Motoneuron-like Cells
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Silvia Sapienza, Valentina Tedeschi, Barbara Apicella, Francesco Palestra, Carmela Russo, Ilaria Piccialli, Anna Pannaccione, Stefania Loffredo, Agnese Secondo, Sapienza, Silvia, Tedeschi, Valentina, Apicella, Barbara, Palestra, Francesco, Russo, Carmela, Piccialli, Ilaria, Pannaccione, Anna, Loffredo, Stefania, and Secondo, Agnese
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Motor Neurons ,Organic Chemistry ,air pollution ,ROS ,General Medicine ,ultrafine particle ,Motor Neuron ,Lysosome ,Catalysis ,Antioxidants ,Computer Science Applications ,Inorganic Chemistry ,ultrafine particles ,TRPML1 ,autophagy ,motor neurons ,neurotoxicity ,lysosome ,mitochondrial dysfunction ,Transient Receptor Potential Channels ,Autophagy ,Particulate Matter ,Physical and Theoretical Chemistry ,Antioxidant ,Lysosomes ,Molecular Biology ,Spectroscopy - Abstract
Background: An emerging body of evidence indicates an association between anthropogenic particulate matter (PM) and neurodegeneration. Although the historical focus of PM toxicity has been on the cardiopulmonary system, ultrafine PM particles can also exert detrimental effects in the brain. However, only a few studies are available on the harmful interaction between PM and CNS and on the putative pathomechanisms. Methods: Ultrafine PM particles with a diameter < 0.1 μm (PM0.1) and nanoparticles < 20 nm (NP20) were sampled in a lab-scale combustion system. Their effect on cell tracking in the space was studied by time-lapse and high-content microscopy in NSC-34 motor neurons while pHrodo™ Green conjugates were used to detect PM endocytosis. Western blotting analysis was used to quantify protein expression of lysosomal channels (i.e., TRPML1 and TPC2) and autophagy markers. Current-clamp electrophysiology and Fura2-video imaging techniques were used to measure membrane potential, intracellular Ca2+ homeostasis and TRPML1 activity in NSC-34 cells exposed to PM0.1 and NP20. Results: NP20, but not PM0.1, reduced NSC-34 motor neuron movement in the space. Furthermore, NP20 was able to shift membrane potential of motor neurons toward more depolarizing values. PM0.1 and NP20 were able to enter into the cells by endocytosis and exerted mitochondrial toxicity with the consequent stimulation of ROS production. This latter event was sufficient to determine the hyperactivation of the lysosomal channel TRPML1. Consequently, both LC3-II and p62 protein expression increased after 48 h of exposure together with AMPK activation, suggesting an engulfment of autophagy. The antioxidant molecule Trolox restored TRPML1 function and autophagy. Conclusions: Restoring TRPML1 function by an antioxidant agent may be considered a protective mechanism able to reestablish autophagy flux in motor neurons exposed to nanoparticles.
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- 2022
8. ApoSOD1 lacking dismutase activity neuroprotects motor neurons exposed to beta-methylamino-L-alanine through the Ca2+/Akt/ERK1/2 prosurvival pathway
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Tiziana Petrozziello, Agnese Secondo, Valentina Tedeschi, Alba Esposito, Maria Josè Sisalli, Gianfranco Di Renzo, Antonella Scorziello, Lucio Annunziato, Petrozziello, Tiziana, Secondo, Agnese, Tedeschi, Valentina, Esposito, Alba, Sisalli, MARIA JOSE', Scorziello, Antonella, DI RENZO, GIANFRANCO MARIA LUIGI, and Annunziato, Lucio
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0301 basic medicine ,Neurodegeneration ,SOD1 ,Cell Biology ,Pharmacology ,Biology ,medicine.disease ,Neuroprotection ,03 medical and health sciences ,030104 developmental biology ,nervous system ,Biochemistry ,medicine ,Neurotoxin ,Dismutase ,Amyotrophic lateral sclerosis ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway - Abstract
Amyotrophic lateral sclerosis (ALS) is a severe human adult-onset neurodegenerative disease affecting lower and upper motor neurons. In >20% of cases, the familial form of ALS is caused by mutations in the gene encoding Cu,Zn-superoxide dismutase (SOD1). Interestingly, administration of wild-type SOD1 to SOD1(G93A) transgenic rats ameliorates motor symptoms through an unknown mechanism. Here we investigated whether the neuroprotective effects of SOD1 are due to the Ca(2+)-dependent activation of such prosurvival signaling pathway and not to its catalytic activity. To this aim, we also examined the mechanism of neuroprotective action of ApoSOD1, the metal-depleted state of SOD1 that lacks dismutase activity, in differentiated motor neuron-like NSC-34 cells and in primary motor neurons exposed to the cycad neurotoxin beta-methylamino-L-alanine (L-BMAA). Preincubation of ApoSOD1 and SOD1, but not of human recombinant SOD1(G93A), prevented cell death in motor neurons exposed to L-BMAA. Moreover, ApoSOD1 elicited ERK1/2 and Akt phosphorylation in motor neurons through an early increase of intracellular Ca(2+) concentration ([Ca(2+)]i). Accordingly, inhibition of ERK1/2 by siMEK1 and PD98059 counteracted ApoSOD1- and SOD1-induced neuroprotection. Similarly, transfection of the dominant-negative form of Akt in NSC-34 motor neurons and treatment with the selective PI3K inhibitor LY294002 prevented ApoSOD1- and SOD1-mediated neuroprotective effects in L-BMAA-treated motor neurons. Furthermore, ApoSOD1 and SOD1 prevented the expression of the two markers of L-BMAA-induced ER stress GRP78 and caspase-12. Collectively, our data indicate that ApoSOD1, which is devoid of any catalytic dismutase activity, exerts a neuroprotective effect through an early activation of Ca(2+)/Akt/ERK1/2 pro-survival pathway that, in turn, prevents ER stress in a neurotoxic model of ALS.
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- 2017
9. The activation of Mucolipin TRP channel 1 (TRPML1) protects motor neurons from L-BMAA neurotoxicity by promoting autophagic clearance
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Agnese Secondo, Tiziana Petrozziello, Valentina Tedeschi, Francesca Boscia, Lorella M.T. Canzoniero, Maria Josè Sisalli, Tedeschi, Valentina, Petrozziello, Tiziana, Sisalli, Maria José, Boscia, Francesca, Canzoniero, Lorella Maria Teresa, and Secondo, Agnese
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0301 basic medicine ,Programmed cell death ,SERCA ,lcsh:Medicine ,Phthalimides ,Hybrid Cells ,Endoplasmic Reticulum ,Molecular neuroscience ,Article ,Mice ,03 medical and health sciences ,Transient Receptor Potential Channels ,0302 clinical medicine ,Autophagy ,medicine ,Animals ,Neurotoxin ,Rats, Wistar ,lcsh:Science ,Endoplasmic Reticulum Chaperone BiP ,Cells, Cultured ,Motor Neurons ,Multidisciplinary ,Cyanobacteria Toxins ,Chemistry ,Endoplasmic reticulum ,Amyotrophic Lateral Sclerosis ,lcsh:R ,Neurotoxicity ,Amino Acids, Diamino ,STIM1 ,medicine.disease ,Rats ,Cell biology ,Disease Models, Animal ,Neuroprotective Agents ,030104 developmental biology ,Quinolines ,Unfolded protein response ,Calcium ,lcsh:Q ,Lysosomes ,030217 neurology & neurosurgery ,Neuroscience - Abstract
Cellular clearance mechanisms including the autophagy-lysosome pathway are impaired in amyotrophic lateral sclerosis (ALS). One of the most important proteins involved in the regulation of autophagy is the lysosomal Ca2+ channel Mucolipin TRP channel 1 (TRPML1). Therefore, we investigated the role of TRPML1 in a neuronal model of ALS/Parkinson-dementia complex reproduced by the exposure of motor neurons to the cyanobacterial neurotoxin beta-methylamino-L-alanine (L-BMAA). Under these conditions, L-BMAA induces a dysfunction of the endoplasmic reticulum (ER) leading to ER stress and cell death. Therefore we hypothesized a dysfunctional coupling between lysosomes and ER in L-BMAA-treated motor neurons. Here, we showed that in motor neuronal cells TRPML1 as well as the lysosomal protein LAMP1 co-localized with ER. In addition, TRPML1 co-immunoprecipitated with the ER Ca2+ sensor STIM1. Functionally, the TRPML1 agonist ML-SA1 induced lysosomal Ca2+ release in a dose-dependent way in motor neuronal cells. The SERCA inhibitor thapsigargin increased the fluorescent signal associated with lysosomal Ca2+ efflux in the cells transfected with the genetically encoded Ca2+ indicator GCaMP3-ML1, thus suggesting an interplay between the two organelles. Moreover, chronic exposure to L-BMAA reduced TRPML1 protein expression and produced an impairment of both lysosomal and ER Ca2+ homeostasis in primary motor neurons. Interestingly, the preincubation of ML-SA1, by an early activation of AMPK and beclin 1, rescued motor neurons from L-BMAA-induced cell death and reduced the expression of the ER stress marker GRP78. Finally, ML-SA1 reduced the accumulation of the autophagy-related proteins p62/SQSTM1 and LC3-II in L-BMAA-treated motor neurons. Collectively, we propose that the pharmacological stimulation of TRPML1 can rescue motor neurons from L-BMAA-induced toxicity by boosting autophagy and reducing ER stress.
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- 2019
10. Calcium Dyshomeostasis and Lysosomal Ca2+ Dysfunction in Amyotrophic Lateral Sclerosis
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Agnese Secondo, Valentina Tedeschi, Tiziana Petrozziello, Tedeschi, Valentina, Petrozziello, Tiziana, and Secondo, Agnese
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amyotrophic lateral sclerosis (ALS) ,ca2+ homeostasis ,Ca2+ homeostasis ,chemistry.chemical_element ,Review ,Mitochondrion ,Calcium ,Endoplasmic Reticulum ,Pathogenesis ,lysosomes ,medicine ,Animals ,Homeostasis ,Humans ,Amyotrophic lateral sclerosis ,lcsh:QH301-705.5 ,Motor Neurons ,Chemistry ,Endoplasmic reticulum ,Amyotrophic Lateral Sclerosis ,Autophagy ,Neurodegeneration ,Ca2+-storing organelles ,Neurodegenerative Diseases ,General Medicine ,medicine.disease ,endoplasmic reticulum (ER) ,Mitochondria ,Cell biology ,Ca2+ homeostasi ,lcsh:Biology (General) ,Ca2+-storing organelle ,ca2+-storing organelles - Abstract
Recent findings in the understanding of amyotrophic lateral sclerosis (ALS) revealed that alteration in calcium (Ca2+) homeostasis may largely contribute to motor neuron demise. A large part of these alterations is due to dysfunctional Ca2+-storing organelles, including the endoplasmic reticulum (ER) and mitochondria. Very recently, lysosomal Ca2+ dysfunction has emerged as an important pathological change leading to neuronal loss in ALS. Remarkably, the Ca2+-storing organelles are interacting with each other at specialized domains controlling mitochondrial dynamics, ER/lysosomal function, and autophagy. This occurs as a result of interaction between specific ionic channels and Ca2+-dependent proteins located in each structure. Therefore, the dysregulation of these ionic mechanisms could be considered as a key element in the neurodegenerative process. This review will focus on the possible role of lysosomal Ca2+ dysfunction in the pathogenesis of several neurodegenerative diseases, including ALS and shed light on the possibility that specific lysosomal Ca2+ channels might represent new promising targets for preventing or at least delaying neurodegeneration in ALS.
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- 2019
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