Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances

Centronuclear myopathies (CNM) are rare congenital disorders characterized by muscle weakness and structural defects including fiber hypotrophy and organelle mispositioning. The main CNM forms are caused by mutations in: the <i>MTM1</i> gene encoding the phosphoinositide phosphatase myot...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Raquel Gómez-Oca, Belinda S. Cowling, Jocelyn Laporte
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	centronuclear myopathy myotubular myopathy myotubularin dynamin amphiphysin ryanodine receptor Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/08539916a47a4d8389490e8ecf59e350
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:08539916a47a4d8389490e8ecf59e350
record_format	dspace
spelling	oai:doaj.org-article:08539916a47a4d8389490e8ecf59e3502021-11-11T16:51:02ZCommon Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances10.3390/ijms2221113771422-00671661-6596https://doaj.org/article/08539916a47a4d8389490e8ecf59e3502021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11377https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Centronuclear myopathies (CNM) are rare congenital disorders characterized by muscle weakness and structural defects including fiber hypotrophy and organelle mispositioning. The main CNM forms are caused by mutations in: the <i>MTM1</i> gene encoding the phosphoinositide phosphatase myotubularin (myotubular myopathy), the <i>DNM2</i> gene encoding the mechanoenzyme dynamin 2, the <i>BIN1</i> gene encoding the membrane curvature sensing amphiphysin 2, and the <i>RYR1</i> gene encoding the skeletal muscle calcium release channel/ryanodine receptor. MTM1, BIN1, and DNM2 proteins are involved in membrane remodeling and trafficking, while RyR1 directly regulates excitation-contraction coupling (ECC). Several CNM animal models have been generated or identified, which confirm shared pathological anomalies in T-tubule remodeling, ECC, organelle mispositioning, protein homeostasis, neuromuscular junction, and muscle regeneration. Dynamin 2 plays a crucial role in CNM physiopathology and has been validated as a common therapeutic target for three CNM forms. Indeed, the promising results in preclinical models set up the basis for ongoing clinical trials. Another two clinical trials to treat myotubular myopathy by MTM1 gene therapy or tamoxifen repurposing are also ongoing. Here, we review the contribution of the different CNM models to understanding physiopathology and therapy development with a focus on the commonly dysregulated pathways and current therapeutic targets.Raquel Gómez-OcaBelinda S. CowlingJocelyn LaporteMDPI AGarticlecentronuclear myopathymyotubular myopathymyotubularindynaminamphiphysinryanodine receptorBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11377, p 11377 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	centronuclear myopathy myotubular myopathy myotubularin dynamin amphiphysin ryanodine receptor Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	centronuclear myopathy myotubular myopathy myotubularin dynamin amphiphysin ryanodine receptor Biology (General) QH301-705.5 Chemistry QD1-999 Raquel Gómez-Oca Belinda S. Cowling Jocelyn Laporte Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances
description	Centronuclear myopathies (CNM) are rare congenital disorders characterized by muscle weakness and structural defects including fiber hypotrophy and organelle mispositioning. The main CNM forms are caused by mutations in: the <i>MTM1</i> gene encoding the phosphoinositide phosphatase myotubularin (myotubular myopathy), the <i>DNM2</i> gene encoding the mechanoenzyme dynamin 2, the <i>BIN1</i> gene encoding the membrane curvature sensing amphiphysin 2, and the <i>RYR1</i> gene encoding the skeletal muscle calcium release channel/ryanodine receptor. MTM1, BIN1, and DNM2 proteins are involved in membrane remodeling and trafficking, while RyR1 directly regulates excitation-contraction coupling (ECC). Several CNM animal models have been generated or identified, which confirm shared pathological anomalies in T-tubule remodeling, ECC, organelle mispositioning, protein homeostasis, neuromuscular junction, and muscle regeneration. Dynamin 2 plays a crucial role in CNM physiopathology and has been validated as a common therapeutic target for three CNM forms. Indeed, the promising results in preclinical models set up the basis for ongoing clinical trials. Another two clinical trials to treat myotubular myopathy by MTM1 gene therapy or tamoxifen repurposing are also ongoing. Here, we review the contribution of the different CNM models to understanding physiopathology and therapy development with a focus on the commonly dysregulated pathways and current therapeutic targets.
format	article
author	Raquel Gómez-Oca Belinda S. Cowling Jocelyn Laporte
author_facet	Raquel Gómez-Oca Belinda S. Cowling Jocelyn Laporte
author_sort	Raquel Gómez-Oca
title	Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances
title_short	Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances
title_full	Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances
title_fullStr	Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances
title_full_unstemmed	Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances
title_sort	common pathogenic mechanisms in centronuclear and myotubular myopathies and latest treatment advances
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/08539916a47a4d8389490e8ecf59e350
work_keys_str_mv	AT raquelgomezoca commonpathogenicmechanismsincentronuclearandmyotubularmyopathiesandlatesttreatmentadvances AT belindascowling commonpathogenicmechanismsincentronuclearandmyotubularmyopathiesandlatesttreatmentadvances AT jocelynlaporte commonpathogenicmechanismsincentronuclearandmyotubularmyopathiesandlatesttreatmentadvances
_version_	1718432220540043264

Common Pathogenic Mechanisms in Centronuclear and Myotubular Myopathies and Latest Treatment Advances

Ejemplares similares