ID 112200
タイトル別表記
Prion accumulation via sortilin dysfunction
著者
キーワード
Prions
prion protein
protein degradation
lysosome
sortilin
sorting
VPS10P sorting receptor
資料タイプ
学術雑誌論文
抄録
Conformational conversion of the cellular prion protein, PrPC, into the abnormally folded isoform of prion protein, PrPSc, which leads to marked accumulation of PrPSc in brains, is a key pathogenic event in prion diseases, a group of fatal neurodegenerative disorders caused by prions. However, the exact mechanism of PrPSc accumulation in prion-infected neurons remains unknown. We recently reported a novel cellular mechanism to support PrPSc accumulation in prion-infected neurons, in which PrPSc 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 PrPSc accumulation in prion-infected neurons, by interacting with PrPC and PrPSc and trafficking them to lysosomes for degradation. However, PrPSc stimulated lysosomal degradation of sortilin, disrupting the sortilin-mediated degradation of PrPC and PrPSc and eventually evoking further accumulation of PrPSc in prion-infected neurons. These findings suggest a positive feedback amplification mechanism for PrPSc accumulation in prion-infected neurons.
掲載誌名
Prion
ISSN
19336896
1933690X
cat書誌ID
AA12489843
出版者
Taylor & Francis
11
6
開始ページ
398
終了ページ
404
発行日
2017-11-15
備考
This is an Accepted Manuscript of an article published by Taylor & Francis in Prion on 15/11/2017, available online: http://www.tandfonline.com/10.1080/19336896.2017.1391435.
EDB ID
337786
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
先端酵素学研究所