Muscular dystrophies are hereditary diseases involving progressive muscular weakness and the degeneration of muscle cells. Several pharmacological treatments have been studied for Duchenne muscular dystrophy (DMD); however, only corticosteroids are currently established therapy. Hori et al. demonstrated that long-term treatment of dystrophin-deficient mdx mice with resveratrol reduced myofiber loss, accompanied by decreased levels of reactive oxygen species (ROS), myofibroblast cells, and fibrosis in the muscles of this genetic model of DMD. These effects of resveratrol are accompanied by decreased oxidative damage in muscles, and suppression of the up-regulation of NADPH oxidase subunits Nox4, Duox1, and p47phox, which results in reduced ROS levels. Even though resveratrol did not reduce the secretion of transforming growth factor-β1 (TGF-β1), it significantly blocked TGF-β1 signal transduction. In C2C12 cells, resveratrol blocked TGF-β1-induced increase in ROS, fibronectin expression (fibrosis), and expression of α-smooth muscle actin; all of these effects of resveratrol were blocked by SIRT1 knockdown. These results suggest a significant therapeutic efficacy of the SIRT1 activator resveratrol in the mdx mouse and that targeting SIRT1 with pharmacological activators might improve the muscle pathology in patients with muscular dystrophies.
See article at J Pharmacol Exp Ther 2011, 338:784–794.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics