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

ABSTRACT: BACKGROUND: ?-Synuclein (?-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 ?-syn transfer. RESULTS: Through a methodology used to obtain synthetic mammalian prions, we tested whether recombinant human ?-syn amyloids can promote prion-like accumulation in neuronal cell lines in vitro. A single exposure to amyloid fibrils of human ?-syn was sufficient to induce aggregation of endogenous ?-syn in human neuroblastoma SH-SY5Y cells. Remarkably, endogenous wild-type ?-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 ?-syn can accumulate in cell culture after a single exposure to exogenous ?-syn short amyloid fibrils. Importantly, using ?-syn short amyloid fibrils as seed, endogenous ?-syn aggregates and accumulates over several passages in cell culture, providing an excellent tool for potential therapeutic screening of pathogenic ?-syn aggregates.

SUBMITTER: Aulic S 

PROVIDER: S-EPMC4064824 | biostudies-other | 2014

REPOSITORIES: biostudies-other