دورية أكاديمية
Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy.
العنوان: | Use of mRNA expression signatures to discover small molecule inhibitors of skeletal muscle atrophy. |
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المؤلفون: | Adams CM; 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., Ebert SM, Dyle MC |
المصدر: | Current opinion in clinical nutrition and metabolic care [Curr Opin Clin Nutr Metab Care] 2015 May; Vol. 18 (3), pp. 263-8. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review |
اللغة: | English |
بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: England NLM ID: 9804399 Publication Model: Print Cited Medium: Internet ISSN: 1473-6519 (Electronic) Linking ISSN: 13631950 NLM ISO Abbreviation: Curr Opin Clin Nutr Metab Care Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1999- : London : Lippincott Williams & Wilkins Original Publication: London ; Philadelphia : Rapid Science Publishers, c1998- |
مواضيع طبية MeSH: | Muscle Proteins/*metabolism , Muscle, Skeletal/*pathology , Muscular Atrophy/*drug therapy , RNA, Messenger/*metabolism , Tomatine/*analogs & derivatives , Triterpenes/*therapeutic use, Drug Discovery/methods ; Gene Expression ; Humans ; Muscle Proteins/genetics ; Muscle, Skeletal/metabolism ; Signal Transduction ; Tomatine/therapeutic use ; Ursolic Acid |
مستخلص: | Purpose of Review: Here, we discuss a recently developed experimental strategy for discovering small molecules with potential to prevent and treat skeletal muscle atrophy. Recent Findings: 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. Summary: Discovery strategies based on mRNA expression signatures can elucidate new approaches for preserving and restoring muscle mass and function. |
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معلومات مُعتمدة: | I01 BX000976 United States BX BLRD VA; R41 AG047684 United States AG NIA NIH HHS; R43 AG044898 United States AG NIA NIH HHS; 1R43AG044898-01 United States AG NIA NIH HHS; F31AG04603801 United States AG NIA NIH HHS; 1R41AG047684-01 United States AG NIA NIH HHS; 5R01AR059115-05 United States AR NIAMS NIH HHS; I01 RX001477 United States RX RRD VA; R01 AR059115 United States AR NIAMS NIH HHS |
المشرفين على المادة: | 0 (Muscle Proteins) 0 (RNA, Messenger) 0 (Triterpenes) 2B73S48786 (tomatidine) 31U6547O08 (Tomatine) |
تواريخ الأحداث: | Date Created: 20150326 Date Completed: 20151217 Latest Revision: 20231213 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC5512448 |
DOI: | 10.1097/MCO.0000000000000159 |
PMID: | 25807353 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1473-6519 |
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DOI: | 10.1097/MCO.0000000000000159 |