Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy

Christopher M Adams; Scott M Ebert; Michael C Dyle

doi:10.1097/MCO.0000000000000159

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Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy

Journal article

Open access

Peer reviewed

Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy

Christopher M Adams, Scott M Ebert and Michael C Dyle

Current opinion in clinical nutrition and metabolic care, Vol.18(3), pp.263-268

05/2015

DOI: 10.1097/MCO.0000000000000159

PMCID: PMC5512448

PMID: 25807353

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Abstract

Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy. Muscle 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. Discovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function.

Gene Expression

Signal Transduction

Humans

Triterpenes - therapeutic use

Drug Discovery - methods

Muscle, Skeletal - metabolism

Tomatine - analogs & derivatives

Muscular Atrophy - drug therapy

RNA, Messenger - metabolism

Muscle Proteins - genetics

Muscle Proteins - metabolism

Tomatine - therapeutic use

Muscle, Skeletal - pathology

Details

Title: Subtitle: Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy
Creators: Christopher M Adams - aDepartment of Internal Medicine, Department of Molecular Physiology and Biophysics, and the Fraternal Order of Eagles Diabetes Research Center, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City bIowa City Veterans Affairs Medical Center, Iowa City cEmmyon, Inc., Coralville, Iowa, USA
Scott M Ebert
Michael C Dyle
Resource Type: Journal article
Publication Details: Current opinion in clinical nutrition and metabolic care, Vol.18(3), pp.263-268
DOI: 10.1097/MCO.0000000000000159
PMID: 25807353
PMCID: PMC5512448
NLM abbreviation: Curr Opin Clin Nutr Metab Care
ISSN: 1363-1950
eISSN: 1473-6519
Publisher: England
Grant note: I01 BX000976 / BLRD VA 1R43AG044898-01 / NIA NIH HHS 1R41AG047684-01 / NIA NIH HHS R43 AG044898 / NIA NIH HHS I01 RX001477 / RRD VA R41 AG047684 / NIA NIH HHS 5R01AR059115-05 / NIAMS NIH HHS R01 AR059115 / NIAMS NIH HHS F31AG04603801 / NIA NIH HHS
Language: English
Date published: 05/2015
Academic Unit: Molecular Physiology and Biophysics; Internal Medicine
Record Identifier: 9984025582102771

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