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

Suzana Aulić (1) , Tran Thanh Nhat Le (1) , Fabio Moda (2) , Saïda Abounit (3) , Stefania Corvaglia (4) , Loredana Casalis (4) , Stefano Gustincich (5) , Chiara Zurzolo (3) , Fabrizio Tagliavini (2) , Giuseppe Legname (1, 4)

1 Laboratory of Prion Biology
2 Division of Neuropathology and Neurology 5
3 Trafic membranaire et Pathogénèse
4 Elettra Sincrotrone Trieste
5 Department of Neuroscience

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.

Domaines: Neurosciences [q-bio.NC]

Suzana Aulić, Tran Thanh Nhat Le, Fabio Moda, Saïda Abounit, Stefania Corvaglia, et al.. Defined α-synuclein prion-like molecular assemblies spreading in cell culture.. BMC Neuroscience, 2014, 15 (1), pp.69. ⟨10.1186/1471-2202-15-69⟩. ⟨pasteur-01010942⟩