期刊
CURRENT OPINION IN CLINICAL NUTRITION AND METABOLIC CARE
卷 18, 期 3, 页码 263-268出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MCO.0000000000000159
关键词
connectivity map; expression signatures; skeletal muscle atrophy; tomatidine; ursolic acid
资金
- National Institutes of Health [5R01AR059115-05, F31AG04603801, 1R43AG044898-01, 1R41AG047684-01]
- Department of Veterans Affairs [5I01BX 000976-05, 1I01RX001477-01]
- Fraternal Order of Eagles Diabetes Research Center at the University of Iowa
- Emmyon, Inc.
Purpose of reviewHere, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy.Recent findingsMuscle atrophy involves and requires widespread changes in skeletal muscle gene expression, which generate complex but measurable patterns of positive and negative changes in skeletal muscle mRNA levels (a.k.a. mRNA expression signatures of muscle atrophy). Many bioactive small molecules generate their own characteristic mRNA expression signatures, and by identifying small molecules whose signatures approximate mirror images of muscle atrophy signatures, one may identify small molecules with potential to prevent and/or reverse muscle atrophy. Unlike a conventional drug discovery approach, this strategy does not rely on a predefined molecular target but rather exploits the complexity of muscle atrophy to identify small molecules that counter the entire spectrum of pathological changes in atrophic muscle. We discuss how this strategy has been used to identify two natural compounds, ursolic acid and tomatidine, that reduce muscle atrophy and improve skeletal muscle function.SummaryDiscovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function.
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