Dino Ferrari Centre, Neuroscience Section, Department of Pathophysiology and Transplantation (DEPT), University of Milan, Via Francesco Sforza 35, 20122, Milan, Italy.
Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Neurology Unit, Via Francesco Sforza 35, 20122, Milan, Italy.
Mol Neurobiol. 2019 Sep;56(9):6460-6471. doi: 10.1007/s12035-019-1533-2. Epub 2019 Mar 4.
Mitofusin 2 (MFN2) is a protein of the mitochondrial outer membrane that belongs to a family of highly conserved dynamin-related GTPases. It is implicated in several intracellular pathways; however, its main role is the regulation of mitochondrial dynamics, in particular mitochondrial fusion. Mutations in MFN2 are associated with Charcot-Marie-Tooth disease type 2A (CMT2A), a neurological disorder characterized by a wide spectrum of clinical features, primarily a motor sensory neuropathy. The cellular and molecular mechanisms by which MFN2 mutations lead to neuronal degeneration are largely unknown, and there is currently no cure for patients. Here, we present the most recent in vitro and in vivo models of CMT2A and the more promising therapeutic approaches under development. These models and therapies may represent relevant tools for the study and recovery of defective mitochondrial dynamics that seem to play a significant role in the pathogenesis of other more common neurodegenerative diseases.
线粒体融合蛋白 2（MFN2）是一种位于线粒体外膜的蛋白质，属于高度保守的动力相关 GTP 酶家族。它参与了几种细胞内途径；然而，其主要作用是调节线粒体动力学，特别是线粒体融合。MFN2 突变与 2A 型腓骨肌萎缩症（CMT2A）有关，这是一种以广泛的临床特征为特征的神经疾病，主要是运动感觉神经病。MFN2 突变导致神经元变性的细胞和分子机制在很大程度上尚不清楚，目前患者尚无治愈方法。在这里，我们介绍了 CMT2A 的最新体外和体内模型以及正在开发的更有前途的治疗方法。这些模型和治疗方法可能代表了研究和恢复有缺陷的线粒体动力学的相关工具，线粒体动力学似乎在其他更常见的神经退行性疾病的发病机制中起着重要作用。
