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International journal of molecular medicine

Role of dystrophin isoforms and associated proteins in muscular dystrophy (review).


PMID 9850730

Abstract

The membrane cytoskeletal component dystrophin and its associated glycoproteins play a central role in the molecular pathogenesis of several muscular dystrophies, i.e. Duchenne/Becker muscular dystrophy, congenital muscular dystrophy and various forms of limb-girdle muscular dystrophy. Although the most frequent of these disorders, Duchenne muscular dystrophy, is mainly recognized as a disease of skeletal muscle fibers, pathophysiological changes also involve the heart and diaphragm, as well as the peripheral and central nervous system. Thus current research efforts into the elucidation of the molecular mechanisms underlying these genetic diseases are not only directed towards studying skeletal muscle necrosis but also investigate abnormalities of heart and brain dystrophin-glycoprotein complexes in cardiomyopathy and brain deficiencies associated with muscular dystrophy. Furthermore, many isoforms of dystrophin and dystrophin-associated components have been identified in various non-muscle tissues and their function(s) are mostly unknown. With respect to skeletal muscle fibers, the characterization of new dystrophin-associated proteins, such as dystrobrevin, sarcospan and the syntrophins, led to a modified model of the spatial configuration of the dystrophin-glycoprotein complex. However, it is generally accepted now that beta-dystroglycan forms the plasmalemma-spanning linkage between dystrophin and the laminin-binding protein alpha-dystroglycan and that this complex is associated with the sarcoglycan subcomplex of sarcolemmal glycoproteins.