Muscular Dystrophy: Disease Mechanisms and Therapies

Progressive weakness and degeneration of skeletal muscles caused by genetic alterations fall into the category of muscular dystrophy. Muscular dystrophy occurs worldwide and affects all races. The overall incidence of muscular dystrophy varies among forms, as some forms are more common than others. Muscle loss and weakness are not necessarily caused by genetic alteration. Skeletal muscle inactivity, denervation, cancer-associated cachexia, and physiological responses to fasting or malnutrition cause skeletal muscle mass loss through imbalance in synthesis and breakdown of proteins. Several genes have been identified that are directly or indirectly involved in various muscle wasting. Studies performed in human and animal models have substantially contributed to our knowledge of molecular mechanism of muscle degeneration but still these findings are inadequate for developing effective therapy. Therefore, precise dissection of molecular mechanisms provides the way for the development of therapeutic interventions for muscular dystrophies as well as for skeletal muscle loss. In this special issue, we intended to publish research and review articles on exploring molecular mechanisms and target identification for treatment of muscle diseases. This issue will give insight into cellular and molecular mechanisms , activation of signaling pathways, how activation of these pathways causes muscle dysfunction, and subsequent disease symptoms. The review article published in this special issue discusses the animal model for muscular dystrophy associated with dystroglycan (F. Sciandra et al.), followed by an article focusing on inflammation status and nutrition in Duchenne muscular dystrophy (DMD) patients (O. R. Cruz-Guzman et al.). The other three articles are related to cellular and molecular modeling of skeletal muscle loss. These articles describe recent advancement in the skeletal muscle research field as well as possibility for developing tools in therapeutic intervention. A study conducted by E. Guadagnin et al. provides new insight into the role of transforming growth factor beta 1 (TGFí µí»½1) in skeletal muscles. TGFí µí»½1 is recently shown to be a key player in skeletal muscle atrophy and endomysial fibrosis. E. Guadagnin et al. demonstrated that TGFí µí»½1 alone can induce Tyr705 phosphorylation of STAT3 in skeletal muscle cells, and higher pSTAT3 (Tyr705) leads to severe phenotype in transgenic TGFí µí»½1 mice. O. R. Cruz-Guzman et al. have shown that chronic inflammation in patients with DMD may be related to loss of muscle function or to obesity. It is not known whether circulating proinflammatory cytokines such as, IL-6, IL-1, and TNF-í µí»¼ levels are associated with muscle function. Therefore, …