A proteasome inhibitor fails to attenuate dystrophic pathology in mdx mice

Dystrophin deficiency leads to increased proteasome activity in skeletal muscle. Previous observations suggest short-term inhibition of the proteasome restores dystrophin expression. Contrary to our hypothesis, eight days of MG-132 administration to mdx mice increased susceptibility to contraction induced injury and Evan’s blue dye penetration compared to controls. Following six weeks of MG-132 administration muscle function was similar to control animals. These data suggest that proteasome inhibition does not reduce the severity of muscle dysfunction caused by dystrophin-deficiency.