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α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication
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(C)) in mediating the uptake and the spread of recombinant α-Syn amyloids. The in vitro data revealed that the...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577263/ https://www.ncbi.nlm.nih.gov/pubmed/28855681 http://dx.doi.org/10.1038/s41598-017-10236-x |
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author | 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 |
author_facet | 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 |
author_sort | Aulić, Suzana |
collection | PubMed |
description | 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(C)) in mediating the uptake and the spread of recombinant α-Syn amyloids. The in vitro data revealed that the presence of PrP(C) fosters the higher uptake of α-Syn amyloid fibrils, which was also confirmed 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 (PrP(Sc)) in vitro and ex vivo, indicating a link between the two proteins. Indeed, whilst PrP(C) is mediating the internalization of α-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 α-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course. |
format | Online Article Text |
id | pubmed-5577263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-55772632017-09-01 α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication 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 Sci Rep Article 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(C)) in mediating the uptake and the spread of recombinant α-Syn amyloids. The in vitro data revealed that the presence of PrP(C) fosters the higher uptake of α-Syn amyloid fibrils, which was also confirmed 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 (PrP(Sc)) in vitro and ex vivo, indicating a link between the two proteins. Indeed, whilst PrP(C) is mediating the internalization of α-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 α-Syn amyloid deposits in Creutzfeldt-Jakob disease patients is accompanied by a longer disease course. Nature Publishing Group UK 2017-08-30 /pmc/articles/PMC5577263/ /pubmed/28855681 http://dx.doi.org/10.1038/s41598-017-10236-x Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article 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 α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
title | α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
title_full | α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
title_fullStr | α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
title_full_unstemmed | α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
title_short | α-Synuclein Amyloids Hijack Prion Protein to Gain Cell Entry, Facilitate Cell-to-Cell Spreading and Block Prion Replication |
title_sort | α-synuclein amyloids hijack prion protein to gain cell entry, facilitate cell-to-cell spreading and block prion replication |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577263/ https://www.ncbi.nlm.nih.gov/pubmed/28855681 http://dx.doi.org/10.1038/s41598-017-10236-x |
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