Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies.
Biochim Biophys Acta
; 1860(1 Pt A): 8-19, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26468903
ABSTRACT
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. GENERALSIGNIFICANCE:
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Corpos de Lewy
/
Alfa-Sinucleína
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Neuroblastoma
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article