Back to Search
Start Over
Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity.
- Source :
-
ELife [Elife] 2019 Dec 17; Vol. 8. Date of Electronic Publication: 2019 Dec 17. - Publication Year :
- 2019
-
Abstract
- 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.<br />Competing Interests: KK, ST, EK, YH, MM, MO, HK, HK, TK, SY, TH, SO No competing interests declared<br /> (© 2019, Kitakaze et al.)
- Subjects :
- Benzothiazoles chemistry
Endoplasmic Reticulum metabolism
Endoplasmic Reticulum Stress drug effects
HEK293 Cells
Humans
Prion Proteins metabolism
Proteostasis drug effects
Unfolded Protein Response drug effects
Benzothiazoles pharmacology
Endoplasmic Reticulum drug effects
High-Throughput Screening Assays methods
Protein Aggregation, Pathological prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 2050-084X
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- ELife
- Publication Type :
- Academic Journal
- Accession number :
- 31843052
- Full Text :
- https://doi.org/10.7554/eLife.43302