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.
|Titolo:||Defined α-synuclein prion-like molecular assemblies spreading in cell culture|
|Autori:||Aulić, S.; Le, T. T.; Moda, F.; Abounit, S.; Corvaglia, S.; Casalis, L.; Gustincich, S.; Zurzolo, C.; Tagliavini, F.; Legname, G.|
|Data di pubblicazione:||2014|
|Digital Object Identifier (DOI):||10.1186/1471-2202-15-69|
|Fulltext via DOI:||10.1186/1471-2202-15-69|
|Appare nelle tipologie:||1.1 Journal article|