Centronuclear myopathies under attack: A plethora of therapeutic targets.
Centronuclear myopathies under attack: A plethora of therapeutic targets.
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DOI：
10.3233/jnd-180309
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发表时间：
2018
影响因子：
3.3
通讯作者：
Laporte J
中科院分区：
文献类型：
--
作者：
Tasfaout H;Cowling BS;Laporte J
中心核肌病是一组以严重的肌肉无力、遗传异质性和肌纤维结构组织缺陷为特征的先天性肌病。它们的名字来源于活检组织中细胞核的中心位置，而在正常情况下，它们位于纤维周围。目前还没有针对这些令人衰弱的疾病的特效药。肌管蛋白磷酸酯酶、GTP酶Dynamin 2或两体蛋白2的突变分别可导致X连锁的中心核肌病(也称为肌管性肌病)或常染色体显性或隐性形式。其他基因的突变，如RYR1、TTN、SpeG或CACNA1S，与可能与中心性肌病重叠的表型有关。在过去的15年里，从无脊椎动物到大型哺乳动物模型，人们研究了许多中心核肌病的动物模型。它们的特征导致了对这些疾病的病理机制的部分了解，并允许最近对治疗概念的验证。在这里，我们回顾了到目前为止已被测试的中心性肌病的不同治疗策略，其中一些可能被翻译成患者。
Centronuclear myopathies are a group of congenital myopathies characterized by severe muscle weakness, genetic heterogeneity, and defects in the structural organization of muscle fibers. Their names are derived from the central position of nuclei on biopsies, while they are at the fiber periphery under normal conditions. No specific therapy exists yet for these debilitating diseases. Mutations in the myotubularin phosphoinositides phosphatase, the GTPase dynamin 2, or amphiphysin 2 have been identified to cause respectively X-linked centronuclear myopathies (also called myotubular myopathy) or autosomal dominant and recessive forms. Mutations in additional genes, as RYR1, TTN, SPEG or CACNA1S, were linked to phenotypes that can overlap with centronuclear myopathies. Numerous animal models of centronuclear myopathies have been studied over the last 15 years, ranging from invertebrate to large mammalian models. Their characterization led to a partial understanding of the pathomechanisms of these diseases and allowed the recent validation of therapeutic proof-of-concepts. Here, we review the different therapeutic strategies that have been tested so far for centronuclear myopathies, some of which may be translated to patients.