title: AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy.
abstract: Recent studies have highlighted the potential of adenosine monophosphate-activated protein kinase (AMPK) to act as a central therapeutic target in Duchenne muscular dystrophy (DMD). Here, we review the role of AMPK as an important integrator of cell signaling pathways that mediate phenotypic plasticity within the context of dystrophic skeletal muscle. Pharmacological AMPK activation remodels skeletal muscle towards a slower, more oxidative phenotype, which is more pathologically resistant to the lack of dystrophin. Moreover, recent studies suggest that AMPK-activated autophagy may be beneficial for myofiber structure and function in mice with muscular dystrophy. Thus, AMPK may represent an ideal target for intervention because clinically approved pharmacological agonists exist, and because benefits can be derived via two independent yet, complementary biological pathways. The availability of several AMPK activators could therefore lead to the rapid development and implementation of novel and highly effective therapeutics aimed at altering the relentless progression of DMD.
authors.affiliation: Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ljubicic
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Jasmin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D006801:Humans; D018485:Muscle Fibers, Skeletal / Q000201:enzymology / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D020388:Muscular Dystrophy, Duchenne / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D010084:Oxidation-Reduction
chemical_list: D055372:AMP-Activated Protein Kinases
keywords: AICAR; AMPK; DMD; autophagy; fiber type; utrophin A