肌营养不良症的Cysteinet失调：致病网络易患治疗

Title:Cysteinet Dysregulation in Muscular Dystrophies: A Pathogenic Network Susceptible to Therapy

Volume: 24 Issue: 3

关键词: 半胱氨酸，硫醇，谷胱甘肽，反应性物质，氧化还原稳态，肌营养不良，乙酰半胱氨酸，线粒体，半胱氨酸。

摘要: Background: Muscular dystrophies are inherited disorders characterized by progressive skeletal muscle degeneration without curative therapy. The specific defective protein in each type of muscular dystrophy has been associated with different deleterious factors that contribute to the progression of the disease. Among these factors, the impairment of calcium homeostasis, the ubiquitin-proteasome dysfunction, and the oxidative damage of cellular macromolecules seem to be of central importance. Can these different cellular dysfunctions be linked by a common pathogenic mechanism susceptible to therapy? A cellular cysteine network (CYSTEINET) has been proposed previously, as a matrix of interconnected sensitive cysteine-containing proteins (SCCPs) that in addition to reactive species and the cysteine/glutathione cycles can regulate metabolic, redox, and survival cellular pathways by a complex biochemical network of proteins with different functions, but sharing the same regulatory thiol group.

Objective: Since there are many sensitive cysteine-containing proteins including cysteinedependent enzymes susceptible to redox modifications at cysteine residues that may contribute to muscular degeneration, the aim of this review is to propose that cysteinet dysregulation may explain oxidative damage, calcium disturbances and ubiquitin-proteasome dysfunctions associated with muscular dystrophies.

Conclusion: The present review proposes that cysteinet dysregulation in muscular dystrophies may represent a common pathogenic network contributing, in association with the specific protein dysfunction, to muscular degeneration. In this context, N-acetylcysteine may have an important role in the restoration of the proposed cysteinet dysregulation associated with these heterogeneous types of diseases.

Cite this article as:

Cysteinet Dysregulation in Muscular Dystrophies: A Pathogenic Network Susceptible to Therapy, Current Medicinal Chemistry 2017; 24 (3) . https://dx.doi.org/10.2174/0929867323666161129124549

DOI https://dx.doi.org/10.2174/0929867323666161129124549	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X