Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases

Research over the last decade strengthened the understanding that skeletal muscles are not only the major tissue in the body from a volume point of view but also function as a master regulator contributing to optimal organismal health. These new contributions to the available body of knowledge trigg...

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Main Authors:	Manring, Heather, Abreu, Eduardo, Brotto, Leticia, Weisleder, Noah, Brotto, Marco
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927072/

id	pubmed-3927072
recordtype	oai_dc
spelling	pubmed-39270722014-03-05 Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases Manring, Heather Abreu, Eduardo Brotto, Leticia Weisleder, Noah Brotto, Marco Physiology Research over the last decade strengthened the understanding that skeletal muscles are not only the major tissue in the body from a volume point of view but also function as a master regulator contributing to optimal organismal health. These new contributions to the available body of knowledge triggered great interest in the roles of skeletal muscle beyond contraction. The World Health Organization, through its Global Burden of Disease (GBD) report, recently raised further awareness about the key importance of skeletal muscles as the GDB reported musculoskeletal (MSK) diseases have become the second greatest cause of disability, with more than 1.7 billion people in the globe affected by a diversity of MSK conditions. Besides their role in MSK disorders, skeletal muscles are also seen as principal metabolic organs with essential contributions to metabolic disorders, especially those linked to physical inactivity. In this review, we have focused on the unique function of new genes/proteins (i.e., MTMR14, MG29, sarcalumenin, KLF15) that during the last few years have helped provide novel insights about muscle function in health and disease, muscle fatigue, muscle metabolism, and muscle aging. Next, we provide an in depth discussion of how these genes/proteins converge into a common function of acting as regulators of intracellular calcium homeostasis. A clear link between dysfunctional calcium homeostasis is established and the special role of store-operated calcium entry is analyzed. The new knowledge that has been generated by the understanding of the roles of previously unknown modulatory genes of the skeletal muscle excitation-contraction coupling (ECC) process brings exciting new possibilities for treatment of MSK diseases, muscle regeneration, and skeletal muscle tissue engineering. The next decade of skeletal muscle and MSK research is bound to bring to fruition applied knowledge that will hopefully offset the current heavy and sad burden of MSK diseases on the planet. Frontiers Media S.A. 2014-02-18 /pmc/articles/PMC3927072/ /pubmed/24600395 http://dx.doi.org/10.3389/fphys.2014.00037 Text en Copyright © 2014 Manring, Abreu, Brotto, Weisleder and Brotto. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Manring, Heather Abreu, Eduardo Brotto, Leticia Weisleder, Noah Brotto, Marco
spellingShingle	Manring, Heather Abreu, Eduardo Brotto, Leticia Weisleder, Noah Brotto, Marco Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
author_facet	Manring, Heather Abreu, Eduardo Brotto, Leticia Weisleder, Noah Brotto, Marco
author_sort	Manring, Heather
title	Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
title_short	Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
title_full	Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
title_fullStr	Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
title_full_unstemmed	Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
title_sort	novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases
description	Research over the last decade strengthened the understanding that skeletal muscles are not only the major tissue in the body from a volume point of view but also function as a master regulator contributing to optimal organismal health. These new contributions to the available body of knowledge triggered great interest in the roles of skeletal muscle beyond contraction. The World Health Organization, through its Global Burden of Disease (GBD) report, recently raised further awareness about the key importance of skeletal muscles as the GDB reported musculoskeletal (MSK) diseases have become the second greatest cause of disability, with more than 1.7 billion people in the globe affected by a diversity of MSK conditions. Besides their role in MSK disorders, skeletal muscles are also seen as principal metabolic organs with essential contributions to metabolic disorders, especially those linked to physical inactivity. In this review, we have focused on the unique function of new genes/proteins (i.e., MTMR14, MG29, sarcalumenin, KLF15) that during the last few years have helped provide novel insights about muscle function in health and disease, muscle fatigue, muscle metabolism, and muscle aging. Next, we provide an in depth discussion of how these genes/proteins converge into a common function of acting as regulators of intracellular calcium homeostasis. A clear link between dysfunctional calcium homeostasis is established and the special role of store-operated calcium entry is analyzed. The new knowledge that has been generated by the understanding of the roles of previously unknown modulatory genes of the skeletal muscle excitation-contraction coupling (ECC) process brings exciting new possibilities for treatment of MSK diseases, muscle regeneration, and skeletal muscle tissue engineering. The next decade of skeletal muscle and MSK research is bound to bring to fruition applied knowledge that will hopefully offset the current heavy and sad burden of MSK diseases on the planet.
publisher	Frontiers Media S.A.
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3927072/
_version_	1612059267864461312

Novel excitation-contraction coupling related genes reveal aspects of muscle weakness beyond atrophy—new hopes for treatment of musculoskeletal diseases

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