The Pathogenesis and Therapies of Striated Muscle Laminopathies.

Astrid Brull,Gisèle Bonne,Blanca Morales Rodriguez,Antoine Muchir,Anne T Bertrand

doi:10.3389/fphys.2018.01533

Abstract

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.

Highlights

Since the first description of a new X-linked muscular disorder by A
This has led to the identification of mutations or variants in genes encoding other nuclear envelope proteins such as FHL1B (Gueneau et al, 2009; Ziat et al, 2016), nesprin 1 and 2 (Zhang et al, 2007), SUN1/2 (Meinke et al, 2014), and LUMA (Liang et al, 2011) associated to a range of muscular dystrophies, some of them sharing clinical features of EmeryDreifuss muscular dystrophy (EDMD)
We showed an altered distribution of Cx43 in LmnaH222P/H222P mice due to microtubule cytoskeleton alteration and decreased acetylation of α-tubulin, leading to electrical conduction disturbances (Macquart et al, 2018)

Summary

Introduction

Since the first description of a new X-linked muscular disorder by A. This has led to the identification of mutations or variants in genes encoding other nuclear envelope proteins such as FHL1B (Gueneau et al, 2009; Ziat et al, 2016), nesprin 1 and 2 (Zhang et al, 2007), SUN1/2 (Meinke et al, 2014), and LUMA (Liang et al, 2011) associated to a range of muscular dystrophies, some of them sharing clinical features of EDMD.

Results

Conclusion