Emerging Strategies Targeting Catabolic Muscle Stress Relief

International Journal of Molecular Sciences

Volker Adams¹  Siegfried Labeit²  T. Scott Bowen³  Mattia Scalabrin³ 

[1] Department of Experimental and Molecular Cardiology, TU Dresden, Heart Center Dresden, 01307 Dresden, Germany;Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany;School of Biomedical Sciences, University of Leeds, LS2 9JT Leeds, UK;

关键词: atrophy;    diaphragm;    disuse;    mitochondria;    MuRF1;    MuRF2;   

DOI  :  10.3390/ijms21134681

来源: DOAJ

【 摘 要 】

Skeletal muscle wasting represents a common trait in many conditions, including aging, cancer, heart failure, immobilization, and critical illness. Loss of muscle mass leads to impaired functional mobility and severely impedes the quality of life. At present, exercise training remains the only proven treatment for muscle atrophy, yet many patients are too ill, frail, bedridden, or neurologically impaired to perform physical exertion. The development of novel therapeutic strategies that can be applied to an in vivo context and attenuate secondary myopathies represents an unmet medical need. This review discusses recent progress in understanding the molecular pathways involved in regulating skeletal muscle wasting with a focus on pro-catabolic factors, in particular, the ubiquitin-proteasome system and its activating muscle-specific E3 ligase RING-finger protein 1 (MuRF1). Mechanistic progress has provided the opportunity to design experimental therapeutic concepts that may affect the ubiquitin-proteasome system and prevent subsequent muscle wasting, with novel advances made in regards to nutritional supplements, nuclear factor kappa-light-chain-enhancer of activated B cells (NFB) inhibitors, myostatin antibodies, β₂ adrenergic agonists, and small-molecules interfering with MuRF1, which all emerge as a novel in vivo treatment strategies for muscle wasting.

【 授权许可】

Unknown