ID | 115090 |
Author |
Kitakaze, Keisuke
Tokushima University|Kawasaki Medical School
Taniuchi, Shusuke
Tokushima University
Kawano, Eri
Tokushima University
Miyake, Masato
Tokushima University
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Kojima, Hirotatsu
The University of Tokyo
Kosako, Hidetaka
Tokushima University
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Kuribara, Tomoko
Tokyo Medical and Dental University
Yoshida, Suguru
Tokyo Medical and Dental University
Hosoya, Takamitsu
Tokyo Medical and Dental University
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Content Type |
Journal Article
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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.
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Journal Title |
eLife
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ISSN | 2050084X
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Publisher | eLife Sciences Publications
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Volume | 8
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Start Page | e43302
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Published Date | 2019-12-17
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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.
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EDB ID | |
DOI (Published Version) | |
URL ( Publisher's Version ) | |
FullText File | |
language |
eng
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TextVersion |
Publisher
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departments |
Institute of Advanced Medical Sciences
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