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

BMC Neuroscience

Giuseppe Legname²  Fabrizio Tagliavini¹  Chiara Zurzolo⁴  Stefano Gustincich⁵  Loredana Casalis²  Stefania Corvaglia²  Saïda Abounit⁴  Fabio Moda¹  Tran Thanh Nhat Le³  Suzana Aulić³ 

[1] Division of Neuropathology and Neurology 5, IRCCS Foundation Carlo Besta Neurological Institute, Via Celoria 11, 20133 Milan, Italy;Elettra-Sincrotrone Trieste S.C.p.A., Area Science Park, 34149 Basovizza, Trieste, Italy;Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), via Bonomea 265, 34136 Trieste, Italy;Trafic Membranaire et Pathogenèse, Biologie des Interactions Cellulaires, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris CEDEX 15, France;Department of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy

关键词: Prion;    Seeding;    Protein aggregation;    α-Synuclein;   

Others  :  799256
DOI  :  10.1186/1471-2202-15-69

 received in 2014-04-03, accepted in 2014-05-22,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Aulić et al.; licensee BioMed Central Ltd.

【 图 表 】

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