title: Cellular and molecular mechanisms of muscle atrophy.
abstract: Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of contractile proteins and organelles in muscle tissue, and discuss how impairments in these mechanisms can contribute to muscle atrophy. We also discuss how protein synthesis and degradation are coordinately regulated by signaling pathways that are influenced by mechanical stress, physical activity, and the availability of nutrients and growth factors. Understanding how these pathways regulate muscle mass will provide new therapeutic targets for the prevention and treatment of muscle atrophy in metabolic and neuromuscular diseases.
authors.affiliation: Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy. bonaldo@bio.unipd.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Bonaldo
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
mesh_terms: D000818:Animals; D001343:Autophagy; D016207:Cytokines / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055435:Myostatin / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D009124:Muscle Proteins; D055435:Myostatin; D025801:Ubiquitin; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex