CHIP as a new target for the treatment and prevention of muscular dystrophies
Muscular dystrophies are a heterogenous group of inherited single-gene disorders, characterized clinically by progressive muscle weakness and wasting. In many cases the molecular basis of a muscular dystrophy is a disruption of the cytoskeleton - extracellular - matrix link, caused by a lack of expression of components of the dystrophin-glycoproteincomplex (DGC).
According to a current model this results in a destabilization of the entire DGC, thereby affecting the structural integrity of the muscle membrane. Duchenne muscular dystrophy (DMD), a severe X-chromosome-linked myopathy, is caused by mutations in the dystrophin gene. Nevertheless, several lines of evidence indicate that dystrophin deficiency is only the first step of a complex pathogenic cascade and much of the late pathology seems to result from ongoing cycles of muscle fiberde- and regeneration. In this respect, characterization of key control components of the de-/regeneration system would open new paths to interfere with the dystrophic process.
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