徳島大学 教育・研究者情報データベース(EDB)

1. 坂口 末廣([徳島大学.先端酵素学研究所.基幹研究部門])

   役割	任意
   貢献度	任意
   学籍番号	推奨

2. 内山 圭司([徳島大学.先端酵素学研究所.重点研究部門])

   役割	任意
   貢献度	任意
   学籍番号	推奨

(英) Novel Amplification Mechanism of Prions through Disrupting Sortilin-Mediated Trafficking.

(英) Conformational conversion of the cellular prion protein, PrP, into the abnormally folded isoform of prion protein, PrP, which leads to marked accumulation of PrP in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrP accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrP accumulation in prion-infected neurons, in which PrP itself promotes its accumulation by evading the cellular inhibitory mechanism, which is newly identified in our recent study. We showed that the VPS10P sorting receptor sortilin negatively regulates PrP accumulation in prion-infected neurons, by interacting with PrP and PrP and trafficking them to lysosomes for degradation. However, PrP stimulated lysosomal degradation of sortilin, disrupting the sortilin-mediated degradation of PrP and PrP and eventually evoking further accumulation of PrP in prion-infected neurons. These findings suggest a positive feedback amplification mechanism for PrP accumulation in prion-infected neurons.

1. (英) Article.ELocationID: 10.1080/19336896.2017.1391435

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) KeywordList.Keyword: Prions

4. (英) KeywordList.Keyword: VPS10P sorting receptor

5. (英) KeywordList.Keyword: lysosome

6. (英) KeywordList.Keyword: prion protein

7. (英) KeywordList.Keyword: protein degradation

8. (英) KeywordList.Keyword: sortilin

9. (英) KeywordList.Keyword: sorting