The precise molecular mechanism of how misfolded Î±-synuclein (Î±-Syn) accumulates and spreads in synucleinopathies is still unknown. Here, we show the role of the cellular prion protein (PrPC) in mediating the uptake and the spread of recombinant Î±-Syn amyloids. The in vitro data revealed that the presence of PrPC fosters the higher uptake of Î±-Syn amyloid fibrils, which was also confirmed in vivo in wild type (Prnp +/+) compared to PrP knock-out (Prnp -/-) mice. Additionally, the presence of Î±-Syn amyloids blocked the replication of scrapie prions (PrPSc) in vitro and ex vivo, indicating a link between the two proteins. Indeed, whilst PrPC is mediating the internalization of Î±-Syn amyloids, PrPSc is not able to replicate in their presence. This observation has pathological relevance, since several reported case studies show that the accumulation of Î±-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course.
|Titolo:||alpha-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication|
|Autori:||Aulić, Suzana; Masperone, Lara; Narkiewicz, Joanna; Isopi, Elisa; Bistaffa, Edoardo; Ambrosetti, Elena; Pastore, Beatrice; De Cecco, Elena; Scaini, Denis; Zago, Paola; Moda, Fabio; Tagliavini, Fabrizio; Legname, Giuseppe|
|Data di pubblicazione:||2017|
|Numero di Articolo:||10050|
|Digital Object Identifier (DOI):||10.1038/s41598-017-10236-x|
|Appare nelle tipologie:||1.1 Journal article|