ID | 115090 |
著者 |
Kitakaze, Keisuke
Tokushima University|Kawasaki Medical School
Taniuchi, Shusuke
Tokushima University
Kawano, Eri
Tokushima University
Kojima, Hirotatsu
The University of Tokyo
Kuribara, Tomoko
Tokyo Medical and Dental University
Yoshida, Suguru
Tokyo Medical and Dental University
Hosoya, Takamitsu
Tokyo Medical and Dental University
|
資料タイプ |
学術雑誌論文
|
抄録 | The endoplasmic reticulum (ER) is responsible for folding secretory and membrane proteins, but disturbed ER proteostasis may lead to protein aggregation and subsequent cellular and clinical pathologies. Chemical chaperones have recently emerged as a potential therapeutic approach for ER stress-related diseases. Here, we identified 2-phenylimidazo[2,1-b]benzothiazole derivatives (IBTs) as chemical chaperones in a cell-based high-throughput screen. Biochemical and chemical biology approaches revealed that IBT21 directly binds to unfolded or misfolded proteins and inhibits protein aggregation. Finally, IBT21 prevented cell death caused by chemically induced ER stress and by a proteotoxin, an aggression-prone prion protein. Taken together, our data show the promise of IBTs as potent chemical chaperones that can ameliorate diseases resulting from protein aggregation under ER stress.
|
掲載誌名 |
eLife
|
ISSN | 2050084X
|
出版者 | eLife Sciences Publications
|
巻 | 8
|
開始ページ | e43302
|
発行日 | 2019-12-17
|
権利情報 | This article is distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
|
EDB ID | |
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 |
出版社版
|
部局 |
先端酵素学研究所
|