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ID 115090
Author
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
Content Type
Journal Article
Description
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.
Journal Title
eLife
ISSN
2050084X
Publisher
eLife Sciences Publications
Volume
8
Start Page
e43302
Published Date
2019-12-17
Rights
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences