Details

Autor(en) / Beteiligte

• Pieri, Laura
• Chafey, Philippe
• Le Gall, Morgane
• Clary, Guilhem
• Melki, Ronald
• Redeker, Virginie

Titel

Cellular response of human neuroblastoma cells to α-synuclein fibrils, the main constituent of Lewy bodies

Ist Teil von

• Biochimica et biophysica acta, 2016-01, Vol.1860 (1), p.8-19

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. Our results show that cells of neuronal origin adapt their proteome to exogenous α-Syn fibrils and actively modify those assemblies. 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. [Display omitted] •Toxic exogenous α-synuclein fibrils induce proteome changes in SH-SY5Y cells.•Regulatory proteins of signaling/apoptosis pathways are overexpressed.•Proteins involved in intracellular vesicle trafficking are overexpressed.•Exogenous α-Syn fibrils are actively modified within recipient cells.