Hallmark Features of the Tropomyosin Regulatory Function in Several Variants of Congenital Myopathy

Congenital myopathies are a group of clinically and genetically heterogeneous diseases, which are united by primary lesions of skeletal muscles and are characterized by progressive muscle weakness and hypotension, as well as morphological changes in muscle tissue. The range of variants of congenital myopathies is quite wide, and their signs are heterogeneous, therefore, the diagnosis is often complicated. Until now, there is no effective therapy for myopathies; only symptomatic treatment is used to improve metabolism and blood microcirculation in the muscles. At the same time, many of these diseases significantly reduce the quality and duration of human life. The accumulation of scientific knowledge for the early diagnosis of human congenital myopathies and the development of approaches for effective treatment of diseases associated with muscle tissue dysfunction is one of the urgent challenges of biology and medicine. Most recently, a series of works has appeared where an attempt has been made to characterize molecular mechanisms involved in etiology and development of a number of myopathies caused by gene mutations of muscle proteins tropomyosin, troponin, nebulin, actin, and some others. It appears extremely important to analyze the published data and, on this basis, highlight critical changes in the conformational state of muscle proteins that can be used as tests for the differential diagnosis of myopathies. This review article is devoted to the analysis and generalization of literature and original data obtained by the method of polarization microfluorimetry on the molecular mechanisms of muscle contraction regulation by mutant tropomyosins that appear in muscle tissue in various human musculoskeletal diseases in order to identify molecular targets for the therapeutic effects.