БИОХИМИЧЕСКИЕ И ПАТОФИЗИОЛОГИЧЕСКИЕ АСПЕКТЫ ДИСФЕРЛИН-АССОЦИИРОВАННЫХ МЫШЕЧНЫХ ДИСТРОФИЙ

Abstract

Dysferlin is a transmembrane calcium-binding protein of the ferlin-1-like protein family, which includes myoferlin Fer1L3, otoferlin Fer1L2 and other ferlins Fer1L4, Fer1L5, and Fer1L6 along with dysferlin itself. Dysferlin is synthesized in all cells of the body, but most actively – in the symplasts of striated muscle tissue. The full range of functions performed by this protein is not fully clarified, but the following have been clearly shown: participation in the post-injury repair of sarcolemma and intracellular vesicular systems, generation and maintenance of the correct functioning of the sarcolemmal T-tubule system, regulation of endo- and exocytosis and inflammation, participation in phagocytosis. Mutations in the dysferlin gene lead to the development of a number of neuromuscular diseases of the autosomal recessive type of inheritance called dysferlinopathies: Miyoshi myopathy, limb-girdle muscular dystrophy type 2B, and distal anterior compartment myopathy. These diseases are characterized by the impaired expression of mRNA and/or the function of the protein dysferlin in skeletal muscles, which is caused by mutations in the DYSF (dystrophy-associated fer-1-like) gene. Although rare, dysferlinopathy is characterized by continuous progression causing severe disability, which explains the importance of research and development of appropriate treatments, including gene therapy. The article presents information on the structure of dysferlin, the mechanisms of its normal functions, as well as the biochemical basis of the pathogenesis of dysferlinopathies.