title: Wasting mechanisms in muscular dystrophy.
abstract: Muscular dystrophy is a group of more than 30 different clinical genetic disorders that are characterized by progressive skeletal muscle wasting and degeneration. Primary deficiency of specific extracellular matrix, sarcoplasmic, cytoskeletal, or nuclear membrane protein results in several secondary changes such as sarcolemmal instability, calcium influx, fiber necrosis, oxidative stress, inflammatory response, breakdown of extracellular matrix, and eventually fibrosis which leads to loss of ambulance and cardiac and respiratory failure. A number of molecular processes have now been identified which hasten disease progression in human patients and animal models of muscular dystrophy. Accumulating evidence further suggests that aberrant activation of several signaling pathways aggravate pathological cascades in dystrophic muscle. Although replacement of defective gene with wild-type is paramount to cure, management of secondary pathological changes has enormous potential to improving the quality of life and extending lifespan of muscular dystrophy patients. In this article, we have reviewed major cellular and molecular mechanisms leading to muscle wasting in muscular dystrophy. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
authors.affiliation: Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
authors.forename: Jonghyun
authors.initials: J
authors.lastname: Shin
authors.forename: Marjan M
authors.initials: MM
authors.lastname: Tajrishi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ogura
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000818:Animals; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B
keywords: CMD; DGC; DMD; Duchenne muscular dystrophy; ECM; IKK; LGMD; MAPK; MMPs; Matrix metalloproteinases; MuRF1; Muscular dystrophy; NF-kappa B; NF-κB; NF-κB-inducing kinase; NIK; NO; Osteopontin; RNS; ROS; TGF-β; TRPC; congenital muscular dystrophy; dystrophin glycoprotein complex; extracellular matrix; inhibitor of I kappa B kinase α; limb-girdle muscular dystrophy; matrix metalloproteinases; mitogen-activated protein kinase; muscle RING-finger protein-1; nitric oxide; nuclear factor-kappa B; reactive nitrogen species; reactive oxygen species; transforming growth factor-β; transient receptor potential canonical