Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics
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,...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
National Academy of Sciences (U.S.)
2016
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| Online Access: | http://hdl.handle.net/1721.1/101110 |
| _version_ | 1810996139129831424 |
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| author | 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 Maetzel, Dorothea Jaenisch, Rudolf Clemons, Paul A. Schreiber, Stuart L. Shamji, Alykhan F. Xavier, Ramnik J. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 Maetzel, Dorothea Jaenisch, Rudolf Clemons, Paul A. Schreiber, Stuart L. Shamji, Alykhan F. Xavier, Ramnik J. |
| author_sort | Kuo, Szu-Yu |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:08:24Z |
| format | Article |
| id | mit-1721.1/101110 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:08:24Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1011102022-10-01T19:27:37Z Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics 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 Maetzel, Dorothea Jaenisch, Rudolf Clemons, Paul A. Schreiber, Stuart L. Shamji, Alykhan F. Xavier, Ramnik J. Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Jaenisch, Rudolf 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. Skoltech Center National Institutes of Health (U.S.) (Grant R01-NS088538) National Institutes of Health (U.S.) (Grant MH104610) 2016-02-05T12:57:03Z 2016-02-05T12:57:03Z 2015-08 2015-05 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/101110 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. en_US http://dx.doi.org/10.1073/pnas.1512289112 Proceedings of the National Academy of Sciences 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. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | 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 Maetzel, Dorothea Jaenisch, Rudolf Clemons, Paul A. Schreiber, Stuart L. Shamji, Alykhan F. Xavier, Ramnik J. Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| title | Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| title_full | Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| title_fullStr | Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| title_full_unstemmed | Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| title_short | Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| title_sort | small molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
| url | http://hdl.handle.net/1721.1/101110 |
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