title: SIRT1: A Novel Target for the Treatment of Muscular Dystrophies.
abstract: Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy and is caused by mutations in the gene that encodes the cytoskeletal protein dystrophin. The treatment for DMD is limited to glucocorticoids, which are associated with multiple side effects. Thus, the identification of novel therapeutic targets is urgently needed. SIRT1 is an NAD(+)-dependent histone/protein deacetylase that plays roles in diverse cellular processes, including stress resistance and cell survival. Studies have shown that SIRT1 activation provides beneficial effects in the dystrophin-deficient mdx mouse, a model of DMD. SIRT1 activation leads to the attenuation of oxidative stress and inflammation, a shift from the fast to slow myofiber phenotype, and the suppression of tissue fibrosis. Although further research is needed to clarify the molecular mechanisms underlying the protective role of SIRT1 in mdx mice, we propose SIRT1 as a novel therapeutic target for patients with muscular dystrophies.
authors.affiliation: Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuno
authors.affiliation: Department of Pharmacology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Horio
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D009136:Muscular Dystrophies / Q000188:drug therapy*; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D056564:Sirtuin 1