Cholesterol metabolism is a potential therapeutic target in Duchenne muscular dystrophy

Autor: Fatima Amor, Ai Vu Hong, Guillaume Corre, Mathilde Sanson, Laurence Suel, Stephanie Blaie, Laurent Servais, Thomas Voit, Isabelle Richard, David Israeli
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Cachexia, Sarcopenia and Muscle, Vol 12, Iss 3, Pp 677-693 (2021)
Druh dokumentu: article
ISSN: 2190-6009
2190-5991
DOI: 10.1002/jcsm.12708
Popis: Abstract Background Duchenne muscular dystrophy (DMD) is a lethal muscle disease detected in approximately 1:5000 male births. DMD is caused by mutations in the DMD gene, encoding a critical protein that links the cytoskeleton and the extracellular matrix in skeletal and cardiac muscles. The primary consequence of the disrupted link between the extracellular matrix and the myofibre actin cytoskeleton is thought to involve sarcolemma destabilization, perturbation of Ca2+ homeostasis, activation of proteases, mitochondrial damage, and tissue degeneration. A recently emphasized secondary aspect of the dystrophic process is a progressive metabolic change of the dystrophic tissue; however, the mechanism and nature of the metabolic dysregulation are yet poorly understood. In this study, we characterized a molecular mechanism of metabolic perturbation in DMD. Methods We sequenced plasma miRNA in a DMD cohort, comprising 54 DMD patients treated or not by glucocorticoid, compared with 27 healthy controls, in three groups of the ages of 4–8, 8–12, and 12–20 years. We developed an original approach for the biological interpretation of miRNA dysregulation and produced a novel hypothesis concerning metabolic perturbation in DMD. We used the mdx mouse model for DMD for the investigation of this hypothesis. Results We identified 96 dysregulated miRNAs (adjusted P‐value
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