Brull Astrid, Morales Rodriguez Blanca, Bonne Gisèle, Muchir Antoine, Bertrand Anne T
Sorbonne Université, INSERM, Institut de Myologie, Center of Research in Myology, UMRS 974, Paris, France.
Sanofi R&D, Chilly Mazarin, France.
Front Physiol. 2018 Oct 30;9:1533. doi: 10.3389/fphys.2018.01533. eCollection 2018.
Emery-Dreifuss muscular dystrophy (EDMD) is a genetic condition characterized by early contractures, skeletal muscle weakness, and cardiomyopathy. During the last 20 years, various genetic approaches led to the identification of causal genes of EDMD and related disorders, all encoding nuclear envelope proteins. By their respective localization either at the inner nuclear membrane or the outer nuclear membrane, these proteins interact with each other and establish a connection between the nucleus and the cytoskeleton. Beside this physical link, these proteins are also involved in mechanotransduction, responding to environmental cues, such as increased tension of the cytoskeleton, by the activation or repression of specific sets of genes. This ability of cells to adapt to environmental conditions is altered in EDMD. Increased knowledge on the pathophysiology of EDMD has led to the development of drug or gene therapies that have been tested on mouse models. This review proposed an overview of the functions played by the different proteins involved in EDMD and related disorders and the current therapeutic approaches tested so far.
埃默里-德赖富斯肌营养不良症（EDMD）是一种遗传性疾病，其特征为早期挛缩、骨骼肌无力和心肌病。在过去20年中，各种基因研究方法已导致鉴定出EDMD及相关疾病的致病基因，这些基因均编码核被膜蛋白。通过各自定位于内核膜或外核膜，这些蛋白质相互作用，并在细胞核与细胞骨架之间建立联系。除了这种物理连接外，这些蛋白质还参与机械转导，通过激活或抑制特定基因集来响应环境信号，如细胞骨架张力增加。EDMD患者细胞的这种适应环境条件的能力发生了改变。对EDMD病理生理学的深入了解已促使开发出在小鼠模型上进行过测试的药物或基因疗法。本综述概述了参与EDMD及相关疾病的不同蛋白质所发挥的功能以及目前已测试的治疗方法。
