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Defined α-synuclein prion-like molecular assemblies spreading in cell culture.

Abstract : BACKGROUND: α-Synuclein (α-syn) plays a central role in the pathogenesis of synucleinopathies, a group of neurodegenerative disorders that includes Parkinson disease, dementia with Lewy bodies and multiple system atrophy. Several findings from cell culture and mouse experiments suggest intercellular α-syn transfer. RESULTS: Through a methodology used to obtain synthetic mammalian prions, we tested whether recombinant human α-syn amyloids can promote prion-like accumulation in neuronal cell lines in vitro. A single exposure to amyloid fibrils of human α-syn was sufficient to induce aggregation of endogenous α-syn in human neuroblastoma SH-SY5Y cells. Remarkably, endogenous wild-type α-syn was sufficient for the formation of these aggregates, and overexpression of the protein was not required. CONCLUSIONS: Our results provide compelling evidence that endogenous α-syn can accumulate in cell culture after a single exposure to exogenous α-syn short amyloid fibrils. Importantly, using α-syn short amyloid fibrils as seed, endogenous α-syn aggregates and accumulates over several passages in cell culture, providing an excellent tool for potential therapeutic screening of pathogenic α-syn aggregates.
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Submitted on : Friday, June 20, 2014 - 9:06:44 PM
Last modification on : Friday, September 18, 2020 - 2:52:03 PM
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Suzana Aulić, Tran Thanh Le, Fabio Moda, Saïda Abounit, Stefania Corvaglia, et al.. Defined α-synuclein prion-like molecular assemblies spreading in cell culture.. BMC Neuroscience, BioMed Central, 2014, 15 (1), pp.69. ⟨10.1186/1471-2202-15-69⟩. ⟨pasteur-01010942⟩

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