Defined α-synuclein prion-like molecular assemblies spreading in cell culture. - Institut Pasteur Access content directly
Journal Articles BMC Neuroscience Year : 2014

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

Suzana Aulić
  • Function : Author
  • PersonId : 957669
Tran Thanh Nhat Le
  • Function : Author
  • PersonId : 957670
Fabio Moda
  • Function : Author
  • PersonId : 957671
Saïda Abounit
  • Function : Author
  • PersonId : 957672
Stefania Corvaglia
  • Function : Author
  • PersonId : 957673
Loredana Casalis
  • Function : Author
  • PersonId : 957674
Stefano Gustincich
  • Function : Author
  • PersonId : 922363
Chiara Zurzolo

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.
Fichier principal
Vignette du fichier
1471-2202-15-69.pdf (935.21 Ko) Télécharger le fichier
1471-2202-15-69-S1.tiff (500.01 Ko) Télécharger le fichier
1471-2202-15-69-S2.docx (17.56 Ko) Télécharger le fichier
1471-2202-15-69-S3.tiff (6.05 Mo) Télécharger le fichier
1471-2202-15-69-S4.tiff (3.16 Mo) Télécharger le fichier
1471-2202-15-69-S5.tiff (1.27 Mo) Télécharger le fichier
1471-2202-15-69-S6.docx (17.1 Ko) Télécharger le fichier
1471-2202-15-69.xml (70.2 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Format : Other
Loading...

Dates and versions

pasteur-01010942 , version 1 (20-06-2014)

Identifiers

Cite

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⟩
74 View
397 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More