Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics
| العنوان: | Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics |
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| المؤلفون: | Gautam Goel, Szu Yu Kuo, Kara L. Conway, Kara G. Lassen, Dorothea Maetzel, Rudolf Jaenisch, Petric Kuballa, Sovan Sarkar, Alykhan F. Shamji, Leslie N. Aldrich, Vlado Dančík, Isabel J. Latorre, Paul A. Clemons, Adam B. Castoreno, Ramnik J. Xavier, Stuart L. Schreiber |
| المصدر: | Proceedings of the National Academy of Sciences. 112 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Genetics, Medical, Green Fluorescent Proteins, Induced Pluripotent Stem Cells, Interleukin-1beta, Cellular homeostasis, Context (language use), Biology, Models, Biological, Small Molecule Libraries, Niemann-Pick C1 Protein, Autophagy, medicine, Humans, Enhancer, Cell Aggregation, Neurons, Membrane Glycoproteins, Multidisciplinary, Bacteria, Neurodegeneration, Intracellular Signaling Peptides and Proteins, Niemann-Pick Disease, Type C, medicine.disease, Phenotype, Human genetics, Cell aggregation, High-Throughput Screening Assays, Cell biology, PNAS Plus, Carrier Proteins, Peptides, HeLa Cells |
| الوصف: | 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. |
| تدمد: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1512289112 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03a055d21881399a769ee1e590baf6c3 https://doi.org/10.1073/pnas.1512289112 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....03a055d21881399a769ee1e590baf6c3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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| DOI: | 10.1073/pnas.1512289112 |