Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics
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Author
Kuo, Szu-Yu
Castoreno, Adam
Aldrich, Leslie
Lassen, Kara
Goel, Gautam
Dančík, Vlado
Kuballa, Petric
Latorre, Isabel
Conway, Kara
Sarkar, Sovan
Maetzel, Dorothea
Jaenisch, Rudolf
Clemons, Paul
Schreiber, Stuart
Shamji, Alykhan
Xavier, Ramnik
Published Version
https://doi.org/10.1073/pnas.1512289112Metadata
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Kuo, Szu-Yu, Adam B. Castoreno, Leslie N. Aldrich, Kara G. Lassen, Gautam Goel, Vlado Dančík, Petric Kuballa, et al. 2015. “Small-Molecule Enhancers of Autophagy Modulate Cellular Disease Phenotypes Suggested by Human Genetics.” Proceedings of the National Academy of Sciences 112 (31): E4281–87. https://doi.org/10.1073/pnas.1512289112.Abstract
Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease.Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:41461204
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