Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies
| Autor: | Morgane Le Gall, Virginie Redeker, Guilhem Clary, Philippe Chafey, Ronald Melki, Laura Pieri |
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| Přispěvatelé: | Institut des Neurosciences de Paris-Saclay ( Neuro-PSI ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences de Paris-Saclay (Neuro-PSI) |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Parkinson's disease Proteome [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology animal diseases Cell Biophysics Biology Fibril Bioinformatics Biochemistry Two-Dimensional Difference Gel Electrophoresis [ SDV.NEU.PC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior 03 medical and health sciences chemistry.chemical_compound Neuroblastoma [ SDV.NEU.SC ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences Cell Line Tumor medicine Humans Molecular Biology Alpha-synuclein [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences Intracellular vesicle medicine.disease Cell biology nervous system diseases 030104 developmental biology medicine.anatomical_structure chemistry nervous system Apoptosis [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology alpha-Synuclein Lewy Bodies Protein Processing Post-Translational |
| Zdroj: | BBA-Biochimica et Biophysica Acta BBA-Biochimica et Biophysica Acta, Elsevier, 2016, 1860 (1 Pt A), pp.8-19. 〈10.1016/j.bbagen.2015.10.007〉 BBA-Biochimica et Biophysica Acta, Elsevier, 2016, 1860 (1 Pt A), pp.8-19. ⟨10.1016/j.bbagen.2015.10.007⟩ |
| ISSN: | 0006-3002 |
| DOI: | 10.1016/j.bbagen.2015.10.007〉 |
| Popis: | Background α-Synuclein (α-Syn) fibrils are the main constituent of Lewy bodies and a neuropathological hallmark of Parkinson's disease (PD). The propagation of α-Syn assemblies from cell to cell suggests that they are involved in PD progression. We previously showed that α-Syn fibrils are toxic because of their ability to bind and permeabilize cell membranes. Here, we document the cellular response in terms of proteome changes of SH-SY5Y cells exposed to exogenous α-Syn fibrils. Methods We compare the proteomes of cells of neuronal origin exposed or not either to oligomeric or fibrillar α-Syn using two dimensional differential in-gel electrophoresis (2D-DIGE) and mass spectrometry. Results Only α-Syn fibrils induce significant changes in the proteome of SH-SY5Y cells. In addition to proteins associated to apoptosis and toxicity, or proteins previously linked to neurodegenerative diseases, we report an overexpression of proteins involved in intracellular vesicle trafficking. We also report a remarkable increase in fibrillar α-Syn heterogeneity, mainly due to C-terminal truncations. Conclusions Our results show that cells of neuronal origin adapt their proteome to exogenous α-Syn fibrils and actively modify those assemblies. General significance Cells of neuronal origin adapt their proteome to exogenous toxic α-Syn fibrils and actively modify those assemblies. Our results bring insights into the cellular response and clearance events the cells implement to face the propagation of α-Syn assemblies associated to pathology. |
| Databáze: | OpenAIRE |
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