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?-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication.

ABSTRACT: The precise molecular mechanism of how misfolded ?-synuclein (?-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 ?-Syn amyloids. The in vitro data revealed that the presence of PrPC fosters the higher uptake of ?-Syn amyloid fibrils, which was also confirmed in vivo in wild type (Prnp +/+) compared to PrP knock-out (Prnp -/-) mice. Additionally, the presence of ?-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 ?-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 ?-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course.

SUBMITTER: Aulic S 

PROVIDER: S-EPMC5577263 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication.

Aulić Suzana S   Masperone Lara L   Narkiewicz Joanna J   Isopi Elisa E   Bistaffa Edoardo E   Ambrosetti Elena E   Pastore Beatrice B   De Cecco Elena E   Scaini Denis D   Zago Paola P   Moda Fabio F   Tagliavini Fabrizio F   Legname Giuseppe G  

Scientific reports 20170830 1

The precise molecular mechanism of how misfolded α-synuclein (α-Syn) accumulates and spreads in synucleinopathies is still unknown. Here, we show the role of the cellular prion protein (PrP<sup>C</sup>) in mediating the uptake and the spread of recombinant α-Syn amyloids. The in vitro data revealed that the presence of PrP<sup>C</sup> fosters the higher uptake of α-Syn amyloid fibrils, which was also confirmed in vivo in wild type (Prnp <sup>+/+</sup>) compared to PrP knock-out (Prnp <sup>-/-</s  ...[more]

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