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首页> 外文期刊>European Journal of Translational Myology >Matrix metalloproteinase activity that disrupt the dystroglycan complex: its role in the molecular pathogenesis of muscular dystrophies
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Matrix metalloproteinase activity that disrupt the dystroglycan complex: its role in the molecular pathogenesis of muscular dystrophies

机译:基质金属蛋白酶活性破坏肌营养不良蛋白复合物:在肌营养不良的分子发病机理中的作用

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摘要

The dystroglycan (DG) complex, composed of two subunits αDG and βDG, interacts with the sarcoglycan complex to form the dystrophin-glycoprotein complex. αDG is a cell surface peripheral membrane protein which binds to the components of the extracellular matrix, while βDG is a type I integral membrane protein which anchors αDG to the cell membrane via the N-terminal extracellular domain. Although defects of the DG gene have not been identified as the primary causes of hereditary diseases in humans, secondary but significant abnormalities of the DG complex have been revealed in a number of muscular dystrophies. In this article, we characterize the matrix metalloproteinase (MMP) activity that disrupts the DG complex by cleaving the extracellular domain of βDG and discuss if this MMP plays a role in the molecular pathogenesis of muscular dystrophies. We also address the therapeutic potential of the drugs that inhibit this MMP activity to decelerate muscle degeneration in these diseases.n
机译:dystroglycan(DG)复合物,由两个亚基αDG和βDG组成,与sarcoglycan复合物相互作用形成肌营养不良蛋白-糖蛋白复合物。 αDG是与细胞外基质成分结合的细胞表面外周膜蛋白,而βDG是通过N端胞外域将αDG锚定至细胞膜的I型整合膜蛋白。尽管尚未确定DG基因的缺陷是人类遗传性疾病的主要原因,但在许多肌肉营养不良中已发现DG复合物的继发性但明显的异常。在本文中,我们描述了通过切割βDG的胞外域来破坏DG复合物的基质金属蛋白酶(MMP)活性,并讨论了该MMP是否在肌肉营养不良的分子发病机理中起作用。我们还探讨了抑制这种MMP活性以减缓这些疾病中肌肉变性的药物的治疗潜力。

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