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EnglishThe 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 (PrPC) in mediating the uptake and the spread of recombinant α-Syn amyloids. The in vitro data revealed that the presence of PrPC fosters the higher uptake of α-Syn amyloid fbrils, which was also confrmed in vivo in wild type (Prnp+/+) compared to PrP knock-out (Prnp−/−) mice. Additionally, the presence of α-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 α-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 α-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course.
| Titolo: | α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
| Autori: | |
| Data di pubblicazione: | 2017 |
| Stato di pubblicazione: | Pubblicato |
| Rivista: | |
| Abstract: | 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 (PrPC) in mediating the uptake and the spread of recombinant α-Syn amyloids. The in vitro data revealed that the presence of PrPC fosters the higher uptake of α-Syn amyloid fbrils, which was also confrmed in vivo in wild type (Prnp+/+) compared to PrP knock-out (Prnp−/−) mice. Additionally, the presence of α-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 α-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 α-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course. |
| Handle: | http://hdl.handle.net/11368/2931308 |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1038/s41598-017-10236-x |
| URL: | https://www.nature.com/articles/s41598-017-10236-x#Sec22 |
| Appare nelle tipologie: | 1.1 Articolo in Rivista |
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| File | Descrizione | Tipologia | Licenza | |
|---|---|---|---|---|
| s41598-017-10236-x.pdf | Documento in Versione Editoriale |  | Open Access Visualizza/Apri | |
| 41598_2017_10236_MOESM1_ESM.pdf | supplementary material | Altro materiale allegato | | Open Access Visualizza/Apri |
