Schiavon Cara R, Shadel Gerald S, Manor Uri
Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA, United States.
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States.
Front Cell Dev Biol. 2021 Feb 1;9:624823. doi: 10.3389/fcell.2021.624823. eCollection 2021.
Charcot-Marie-Tooth (CMT) disease is a progressive, peripheral neuropathy and the most commonly inherited neurological disorder. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility, suggesting that organelle trafficking defects may be a common underlying disease mechanism. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the conceptional challenges and potential experimental and therapeutic opportunities presented by this "impaired mobility" model of the disease.
夏科-马里-图斯（CMT）病是一种进行性周围神经病变，也是最常见的遗传性神经疾病。CMT突变的临床表现通常仅限于周围神经元，即人体中最长的细胞。目前，至少80种不同基因的突变与CMT相关，并且新的突变也在不断被发现。在轴索性CMT中发生突变的很大一部分蛋白质在线粒体移动性方面具有已记录的作用，这表明细胞器运输缺陷可能是一种常见的潜在疾病机制。本综述将聚焦线粒体移动性改变在轴索性CMT发病机制中的潜在作用，强调这种疾病的“移动性受损”模型所带来的概念性挑战以及潜在的实验和治疗机会。
