Abstract

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.

中文翻译：

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几种先天性肌病变异体中原肌球蛋白调节功能的标志性特征

摘要

先天性肌病是一组临床和遗传异质性疾病，由骨骼肌原发病变联合而成，以进行性肌无力和低血压以及肌肉组织形态学改变为特征。先天性肌病的变异范围相当广泛，其体征具有异质性，因此诊断往往较为复杂。到目前为止，还没有有效的治疗肌病的方法。只有对症治疗才能改善肌肉的新陈代谢和血液微循环。与此同时，许多这些疾病显着降低了人类的生活质量和持续时间。为人类先天性肌病的早期诊断积累科学知识以及开发有效治疗与肌肉组织功能障碍相关的疾病的方法是生物学和医学的紧迫挑战之一。最近，出现了一系列工作，试图描述由肌肉蛋白原肌球蛋白、肌钙蛋白、nebulin、肌动蛋白和其他一些基因突变引起的许多肌病的病因和发展的分子机制。分析已发表的数据似乎极其重要，并在此基础上突出肌肉蛋白质构象状态的关键变化，可用作肌病鉴别诊断的测试。