Potential Therapeutic Strategies for Skeletal Muscle Atrophy

Abstract

The maintenance of muscle homeostasis is vital for life and health. Skeletal muscle atrophy not only seriously reduces people’s quality of life and increases morbidity and mortality, but also causes a huge socioeconomic burden. To date, no effective treatment has been developed for skeletal muscle atrophy owing to an incomplete understanding of its molecular mechanisms. Exercise therapy is the most effective treatment for skeletal muscle atrophy. Unfortunately, it is not suitable for all patients, such as fractured patients and bedridden patients with nerve damage. Therefore, understanding the molecular mechanism of skeletal muscle atrophy is crucial for developing new therapies for skeletal muscle atrophy. In this review, PubMed was systematically screened for articles that appeared in the past 5 years about potential therapeutic strategies for skeletal muscle atrophy. Herein, we summarize the roles of inflammation, oxidative stress, ubiquitin-proteasome system, autophagic-lysosomal pathway, caspases, and calpains in skeletal muscle atrophy and systematically expound the potential drug targets and therapeutic progress against skeletal muscle atrophy. This review focuses on current treatments and strategies for skeletal muscle atrophy, including drug treatment (active substances of traditional Chinese medicine, chemical drugs, antioxidants, enzyme and enzyme inhibitors, hormone drugs, etc.), gene therapy, stem cell and exosome therapy (muscle-derived stem cells, non-myogenic stem cells, and exosomes), cytokine therapy, physical therapy (electroacupuncture, electrical stimulation, optogenetic technology, heat therapy, and low-level laser therapy), nutrition support (protein, essential amino acids, creatine, β-hydroxy-β-methylbutyrate, and vitamin D), and other therapies (biomaterial adjuvant therapy, intestinal microbial regulation, and oxygen supplementation). Considering many treatments have been developed for skeletal muscle atrophy, we propose a combination of proper treatments for individual needs, which may yield better treatment outcomes.

Mitochondrial dysfunction: roles in skeletal muscle atrophy

“…Muscle atrophy F-box (MAFbx) and muscle RING-finger protein-1 (MuRF1) are two muscle-specific E3 ubiquitin ligases in the UPS. During muscle atrophy, they are specifically expressed and target specific protein substrates for degradation in the UPS [ 7 , 8 ]. The ALP is another important proteolysis system that removes misfolded or other harmful proteins, but its overactivation can lead to muscle atrophy [ 9 ].…”

Vitamin C regulates skeletal muscle post-injury regeneration by promoting myoblast proliferation through its direct interaction with the Pax7 protein

“…However, whether early supplementation of VC can prevent the occurrence of muscle atrophy before the onset of muscle atrophy remains unclear, which deserves further study. 31 It is interesting that VC has promoted the upregulation of proliferating markers before inducing atrophy and injury, indicating that VC may stimulate the proliferation of MuSCs in the quiescent state of muscles. Over all, VC can provide new ideas and strategies for the prevention and treatment of muscle atrophy, which has potential application value.…”

Impact of Chinese herbal medicine on sarcopenia in enhancing muscle mass, strength, and function: A systematic review and meta‐analysis of randomized controlled trials

“…As an essential part of TCM, Chinese herbal medicine has been widely used around the world. Based on the theory of “bian zheng lun zhi” and Chinese philosophy, Chinese herbal medicine has long been used to treat sarcopenia (Guo et al, 2022) and its complications like muscle atrophy (Huang et al, 2022). Additionally, the beneficial therapeutic effects of herbal medicine in sarcopenia have also been proved in the sarcopenic animal models (Ding et al, 2023).…”