Defined α-synuclein prion-like molecular assemblies spreading in cell culture
- Equal contributors
1 Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), via Bonomea 265, 34136 Trieste, Italy
2 Division of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy
3 Trafic Membranaire et Pathogenèse, Biologie des Interactions Cellulaires, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris CEDEX 15, France
4 Elettra-Sincrotrone Trieste S.C.p.A., Area Science Park, 34149 Basovizza, Trieste, Italy
5 Department of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy
BMC Neuroscience 2014, 15:69 doi:10.1186/1471-2202-15-69Published: 4 June 2014
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.
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.
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.