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DRCL RESEARCH: Emerging Strategies Targeting Catabolic Muscle Stress Relief

Mattia Scalabrin 1, Volker Adams 2,3, Siegfried Labeit 4,5 and T. Scott Bowen 1,*
1 School of Biomedical Sciences, University of Leeds, LS2 9JT Leeds, UK; M.Scalabrin@leeds.ac.uk
2 Department of Experimental and Molecular Cardiology, TU Dresden, Heart Center Dresden,
01307 Dresden, Germany; volker.adams@mailbox.tu-dresden.de
3 Dresden Cardiovascular Research Institute and Core Laboratories GmbH, 01067 Dresden, Germany
4 Medical Faculty Mannheim, University of Heidelberg, 68167 Mannheim, Germany; labeit@medma.de
5 Myomedix GmbH, Im Biengarten 36, 69151 Neckargemünd, Germany
* Correspondence: T.S.Bowen@leeds.ac.uk
Received: 4 June 2020; Accepted: 29 June 2020; Published: 30 June 2020
Abstract: 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 RINGfinger
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 (NFB) 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.