sarcospan 在黏附复合物替换治疗肌营养不良症中的潜力。
The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.
机构信息
Department of Integrative Biology and Physiology, University of California, Los Angeles, CA 90095, USA.
出版信息
FEBS J. 2013 Sep;280(17):4210-29. doi: 10.1111/febs.12295. Epub 2013 May 13.
Abstract
Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic.
摘要
三个黏附复合物跨越肌膜，促进细胞外基质与肌动蛋白细胞骨架之间的关键连接：dystrophin 和 utrophin-糖蛋白复合物以及 α7β1 整合素。单个蛋白成分的缺失会导致整个蛋白复合物的缺失和肌肉营养不良。肌肉营养不良是一种进行性、致命性的消耗性疾病，其特征是肌纤维反复退化和再生。蛋白质替代疗法为肌肉营养不良的治疗提供了一种很有前途的方法。最近，我们证明 sarcospan 促进黏附复合物之间的蛋白-蛋白相互作用，是一个重要的潜在治疗靶点。在这里，我们回顾了当前的蛋白质替代策略，讨论了 sarcospan 表达的潜在益处，并确定了 sarcospan 进入临床前必须解决的重要实验。
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