title: Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia.
abstract: Muscle atrophy-also known as muscle wasting-is a debilitating syndrome that slowly develops with age (sarcopenia) or rapidly appears at the late stages of deadly diseases such as cancer, AIDS, and sepsis (cachexia). Despite the prevalence and the drastic detrimental effects of these two syndromes, there are currently no widely used, effective treatment options for those suffering from muscle wasting. In an attempt to identify potential therapeutic targets, the molecular mechanisms of sarcopenia and cachexia have begun to be elucidated. Growing evidence suggests that inflammatory cytokines may play an important role in the pathology of both syndromes. As one of the key cytokines involved in both sarcopenic and cachectic muscle wasting, tumor necrosis factor α (TNFα) and its downstream effectors provide an enticing target for pharmacological intervention. However, to date, no drugs targeting the TNFα signaling pathway have been successful as a remedial option for the treatment of muscle wasting. Thus, there is a need to identify new effectors in this important pathway that might prove to be more efficacious targets. Inducible nitric oxide synthase (iNOS) has recently been shown to be an important mediator of TNFα-induced cachectic muscle loss, and studies suggest that it may also play a role in sarcopenia. In addition, investigations into the mechanism of iNOS-mediated muscle loss have begun to reveal potential therapeutic strategies. In this review, we will highlight the potential for targeting the iNOS/NO pathway in the treatment of muscle loss and discuss its functional relevance in sarcopenia and cachexia.
authors.affiliation: McGill University, Biochemistry Department, Goodman Cancer Center, Montreal, Canada.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Hall
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Ma
authors.forename: Sergio Di
authors.initials: SD
authors.lastname: Marco
authors.forename: Imed-Eddine
authors.initials: IE
authors.lastname: Gallouzi
mesh_terms: D000375:Aging / Q000502:physiology*; D002100:Cachexia / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D009133:Muscular Atrophy / Q000201:enzymology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D055948:Sarcopenia / Q000201:enzymology*
chemical_list: D052247:Nitric Oxide Synthase Type II