title: Defined α-synuclein prion-like molecular assemblies spreading in cell culture.
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.
authors.forename: Suzana
authors.initials: S
authors.lastname: Aulić
authors.forename: Tran Thanh Nhat
authors.initials: TT
authors.lastname: Le
authors.forename: Fabio
authors.initials: F
authors.lastname: Moda
authors.forename: Saïda
authors.initials: S
authors.lastname: Abounit
authors.forename: Stefania
authors.initials: S
authors.lastname: Corvaglia
authors.forename: Loredana
authors.initials: L
authors.lastname: Casalis
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
authors.forename: Chiara
authors.initials: C
authors.lastname: Zurzolo
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Tagliavini
authors.affiliation: Laboratory of Prion Biology, Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), via Bonomea 265, 34136 Trieste, Italy. legname@sissa.it.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Legname
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D011328:Prions / Q000145:classification* / Q000378:metabolism*; D051844:alpha-Synuclein / Q000145:classification* / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D011328:Prions; D051844:alpha-Synuclein