TY - JOUR
T1 - Abnormal Calcium Handling in Duchenne Muscular Dystrophy
T2 - Mechanisms and Potential Therapies
AU - Mareedu, Satvik
AU - Million, Emily D.
AU - Duan, Dongsheng
AU - Babu, Gopal J.
N1 - Funding Information:
This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, US National Institutes of Health (NIH) grant (Grant #1R01AR069107 to GB, Grant # 1R01AR070517 to DD and GB), Jesse’s Journey: The Foundation for Gene and Cell Therapy (to DD and GB), and Jackson Freel DMD Research Fund (to DD). EM was supported by the University of Missouri Life Science Fellowship.
Publisher Copyright:
© Copyright © 2021 Mareedu, Million, Duan and Babu.
PY - 2021/4/9
Y1 - 2021/4/9
N2 - Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by the loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fatty replacement, and fibrosis, resulting in muscle weakness, respiratory and cardiac failure, and premature death. There is no curative treatment. Investigations on disease-causing mechanisms offer an opportunity to identify new therapeutic targets to treat DMD. An abnormal elevation of the intracellular calcium ( (Formula presented.) ) concentration in the dystrophin-deficient muscle is a major secondary event, which contributes to disease progression in DMD. Emerging studies have suggested that targeting Ca2+-handling proteins and/or mechanisms could be a promising therapeutic strategy for DMD. Here, we provide an updated overview of the mechanistic roles the sarcolemma, sarcoplasmic/endoplasmic reticulum, and mitochondria play in the abnormal and sustained elevation of (Formula presented.) levels and their involvement in DMD pathogenesis. We also discuss current approaches aimed at restoring Ca2+ homeostasis as potential therapies for DMD.
AB - Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by the loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fatty replacement, and fibrosis, resulting in muscle weakness, respiratory and cardiac failure, and premature death. There is no curative treatment. Investigations on disease-causing mechanisms offer an opportunity to identify new therapeutic targets to treat DMD. An abnormal elevation of the intracellular calcium ( (Formula presented.) ) concentration in the dystrophin-deficient muscle is a major secondary event, which contributes to disease progression in DMD. Emerging studies have suggested that targeting Ca2+-handling proteins and/or mechanisms could be a promising therapeutic strategy for DMD. Here, we provide an updated overview of the mechanistic roles the sarcolemma, sarcoplasmic/endoplasmic reticulum, and mitochondria play in the abnormal and sustained elevation of (Formula presented.) levels and their involvement in DMD pathogenesis. We also discuss current approaches aimed at restoring Ca2+ homeostasis as potential therapies for DMD.
KW - Duchenne muscular dystrophy
KW - calcium
KW - dystrophin
KW - mitochondria
KW - ryanodine receptor
KW - sarco(endo)plasmic reticulum calcium ATPase
KW - sarcolemma
KW - sarcolipin
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U2 - 10.3389/fphys.2021.647010
DO - 10.3389/fphys.2021.647010
M3 - Review article
AN - SCOPUS:85104574938
VL - 12
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 647010
ER -