| First Author | Aulić S | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 10050 |
| PubMed ID | 28855681 | Mgi Jnum | J:256452 |
| Mgi Id | MGI:6108412 | Doi | 10.1038/s41598-017-10236-x |
| Citation | Aulic S, et al. (2017) alpha-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication. Sci Rep 7(1):10050 |
| abstractText | The precise molecular mechanism of how misfolded alpha-synuclein (alpha-Syn) accumulates and spreads in synucleinopathies is still unknown. Here, we show the role of the cellular prion protein (PrP(C)) in mediating the uptake and the spread of recombinant alpha-Syn amyloids. The in vitro data revealed that the presence of PrP(C) fosters the higher uptake of alpha-Syn amyloid fibrils, which was also confirmed in vivo in wild type (Prnp (+/+)) compared to PrP knock-out (Prnp (-/-)) mice. Additionally, the presence of alpha-Syn amyloids blocked the replication of scrapie prions (PrP(Sc)) in vitro and ex vivo, indicating a link between the two proteins. Indeed, whilst PrP(C) is mediating the internalization of alpha-Syn amyloids, PrP(Sc) is not able to replicate in their presence. This observation has pathological relevance, since several reported case studies show that the accumulation of alpha-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course. |
