Immune-Mediated Mechanisms Potentially Regulate the Disease Time-Course of Duchenne Muscular Dystrophy and Provide Targets for Therapeutic Intervention

Duchenne muscular dystrophy is a lethal muscle-wasting disease that affects boys. Mutations in the dystrophin gene result in the absence of the dystrophin glycoprotein complex (DGC) from muscle plasma membranes. In healthy muscle fibers, the DGC forms a link between the extracellular matrix and the...

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Bibliographic Details
Published in:PM & R 2009-08, Vol.1 (8), p.755-768
Main Authors: Evans, Nicholas P., BS, Misyak, Sarah A., MS, Robertson, John L., PhD, VMD, Bassaganya-Riera, Josep, PhD, DVM, Grange, Robert W., PhD
Format: Article
Language:English
Subjects:
Age Factors
Animals
Cytokines - physiology
Humans
Mice
Mice, Inbred mdx
Muscular Dystrophy, Duchenne - immunology
Muscular Dystrophy, Duchenne - pathology
Muscular Dystrophy, Duchenne - therapy
NF-kappa B - physiology
Physical Medicine and Rehabilitation
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Summary:Duchenne muscular dystrophy is a lethal muscle-wasting disease that affects boys. Mutations in the dystrophin gene result in the absence of the dystrophin glycoprotein complex (DGC) from muscle plasma membranes. In healthy muscle fibers, the DGC forms a link between the extracellular matrix and the cytoskeleton to protect against contraction-induced membrane lesions and to regulate cell signaling. The absence of the DGC results in aberrant regulation of inflammatory signaling cascades. Inflammation is a key pathological characteristic of dystrophic muscle lesion formation. However, the role and regulation of this process in the disease time-course has not been sufficiently examined. The transcription factor nuclear factor-κB has been shown to contribute to the disease process and is likely involved with increased inflammatory gene expression, including cytokines and chemokines, found in dystrophic muscle. These aberrant signaling processes may regulate the early time-course of inflammatory events that contribute to the onset of disease. This review critically evaluates the possibility that dystrophic muscle lesions in both patients with Duchenne muscular dystrophy and mdx mice are the result of immune-mediated mechanisms that are regulated by inflammatory signaling and also highlights new therapeutic directions.
ISSN:1934-1482
1934-1563
DOI:10.1016/j.pmrj.2009.04.010