Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics
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Kuo-2015-Small-molecule enhan.pdf
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Author(s)
Kuo, Szu-Yu
Castoreno, Adam B.
Aldrich, Leslie N.
Lassen, Kara G.
Goel, Gautam
Dancik, Vlado
Kuballa, Petric
Latorre, Isabel
Conway, Kara L.
Sarkar, Sovan
Date Issued
August 2015
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Kuo, Szu-Yu, Adam B. Castoreno, Leslie N. Aldrich, Kara G. Lassen, Gautam Goel, Vlado Dancik, Petric Kuballa, et al. “Small-Molecule Enhancers of Autophagy Modulate Cellular Disease Phenotypes Suggested by Human Genetics.” Proc Natl Acad Sci USA 112, no. 31 (July 20, 2015): E4281–E4287.
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Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1512289112
