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Open Access Highly Accessed Research article

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

Suzana Aulić1, Tran Thanh Nhat Le1, Fabio Moda2, Saïda Abounit3, Stefania Corvaglia4, Loredana Casalis4, Stefano Gustincich5, Chiara Zurzolo3, Fabrizio Tagliavini2 and Giuseppe Legname14*

  • * Corresponding author: Giuseppe Legname legname@sissa.it

  • † Equal contributors

Author Affiliations

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

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BMC Neuroscience 2014, 15:69  doi:10.1186/1471-2202-15-69

Published: 4 June 2014

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.

Keywords:
α-Synuclein; Protein aggregation; Seeding; Prion