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Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences

1
Molecular Biology Unit, Mossakowski Medical Research Institute Polish Academy of Sciences, 02-106 Warsaw, Poland
2
School of Pharmacy and Biomedical Sciences, University of Portsmouth, St Michael’s Building, White Swan Road, Portsmouth PO1 2DT, UK
3
Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland
4
Laboratory of Cellular Metabolism, Nencki Institute of Experimental Biology Polish Academy of Sciences, 02-093 Warsaw, Poland
*
Authors to whom correspondence should be addressed.
Academic Editor: Jose Javier Lopez
Int. J. Mol. Sci. 2021, 22(20), 11040; https://doi.org/10.3390/ijms222011040
Received: 12 September 2021 / Revised: 30 September 2021 / Accepted: 9 October 2021 / Published: 13 October 2021
(This article belongs to the Section Biochemistry)
Duchenne muscular dystrophy (DMD) leads to disability and death in young men. This disease is caused by mutations in the DMD gene encoding diverse isoforms of dystrophin. Loss of full-length dystrophins is both necessary and sufficient for causing degeneration and wasting of striated muscles, neuropsychological impairment, and bone deformities. Among this spectrum of defects, abnormalities of calcium homeostasis are the common dystrophic feature. Given the fundamental role of Ca2+ in all cells, this biochemical alteration might be underlying all the DMD abnormalities. However, its mechanism is not completely understood. While abnormally elevated resting cytosolic Ca2+ concentration is found in all dystrophic cells, the aberrant mechanisms leading to that outcome have cell-specific components. We probe the diverse aspects of calcium response in various affected tissues. In skeletal muscles, cardiomyocytes, and neurons, dystrophin appears to serve as a scaffold for proteins engaged in calcium homeostasis, while its interactions with actin cytoskeleton influence endoplasmic reticulum organisation and motility. However, in myoblasts, lymphocytes, endotheliocytes, and mesenchymal and myogenic cells, calcium abnormalities cannot be clearly attributed to the loss of interaction between dystrophin and the calcium toolbox proteins. Nevertheless, DMD gene mutations in these cells lead to significant defects and the calcium anomalies are a symptom of the early developmental phase of this pathology. As the impaired calcium homeostasis appears to underpin multiple DMD abnormalities, understanding this alteration may lead to the development of new therapies. In fact, it appears possible to mitigate the impact of the abnormal calcium homeostasis and the dystrophic phenotype in the total absence of dystrophin. This opens new treatment avenues for this incurable disease. View Full-Text
Keywords: Duchenne muscular dystrophy; calcium signalling; calcium homeostasis; mitochondria; endoplasmic reticulum Duchenne muscular dystrophy; calcium signalling; calcium homeostasis; mitochondria; endoplasmic reticulum
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MDPI and ACS Style

Zabłocka, B.; Górecki, D.C.; Zabłocki, K. Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences. Int. J. Mol. Sci. 2021, 22, 11040. https://doi.org/10.3390/ijms222011040

AMA Style

Zabłocka B, Górecki DC, Zabłocki K. Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences. International Journal of Molecular Sciences. 2021; 22(20):11040. https://doi.org/10.3390/ijms222011040

Chicago/Turabian Style

Zabłocka, Barbara, Dariusz C. Górecki, and Krzysztof Zabłocki. 2021. "Disrupted Calcium Homeostasis in Duchenne Muscular Dystrophy: A Common Mechanism behind Diverse Consequences" International Journal of Molecular Sciences 22, no. 20: 11040. https://doi.org/10.3390/ijms222011040

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