Simvastatin offers new prospects for the treatment of Duchenne muscular dystrophy.
Simvastatin offers new prospects for the treatment of Duchenne muscular dystrophy.
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DOI：
10.1080/21675511.2016.1156286
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Froehner SC
中科院分区：
文献类型：
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作者：
Whitehead NP;Kim MJ;Bible KL;Adams ME;Froehner SC
Duchenne肌营养不良症(DMD)是最常见、最严重的遗传性神经肌肉疾病。DMD是由肌肉纤维中的肌营养不良蛋白编码基因突变引起的。Dystrophin最初被认为是一种结构蛋白，可以保护肌膜免受收缩过程中产生的压力。然而，最近的实验证据揭示了一个复杂得多的图景，dystrophin的丢失导致了多个肌肉信号通路的功能障碍，这些都参与了整个疾病的病理生理学。目前基于基因的治疗DMD的方法在概念上很有吸引力，因为它们提供了将肌营养不良蛋白恢复到肌肉的可能性，尽管它是一种部分功能的、截断的蛋白质形式。然而，考虑到这些遗传方法面临的成本和技术挑战，重要的是考虑是否可以将相对便宜的临床使用的药物重新用于治疗DMD。在这里，我们讨论我们的最新发现，显示辛伐他汀作为一种治疗DMD的新疗法的潜力。
Duchenne muscular dystrophy (DMD) is the most common and severe inherited neuromuscular disorder. DMD is caused by mutations in the gene encoding the dystrophin protein in muscle fibers. Dystrophin was originally proposed to be a structural protein that protected the sarcolemma from stresses produced during contractions. However, more recently, experimental evidence has revealed a far more complicated picture, with the loss of dystrophin causing dysfunction of multiple muscle signaling pathways, which all contribute to the overall disease pathophysiology. Current gene-based approaches for DMD are conceptually appealing since they offer the potential to restore dystrophin to muscles, albeit a partially functional, truncated form of the protein. However, given the cost and technical challenges facing these genetic approaches, it is important to consider if relatively inexpensive, clinically used drugs may be repurposed for treating DMD. Here, we discuss our recent findings showing the potential of simvastatin as a novel therapy for DMD.