title: Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.
abstract: Remote neuronal degeneration and death/injury, which often occur in regions remote but functionally connected to the primary lesion site, may play a pivotal role in extending neuronal damage/dysfunction following traumatic brain injury, stroke, or peripheral nerve injury, as well as in chronic neurodegenerative diseases such as multiple sclerosis and amyotrophic lateral sclerosis. Even though the precise mechanisms of remote neuronal injury are poorly understood and no efficacious treatment options are available, it involves glial activation, inflammation, oxidative/nitrative stress, and apoptotic cell death. The newly discovered endocannabinoid signaling system consisting of endocannabinoids (endogenous bioactive lipid mediators), their synthetic and metabolizing enzymes, and their primary G protein-coupled cannabinoid 1 and 2 (CB(1) and CB(2)) receptors has been implicated in the regulation of numerous physiological and pathological processes/functions, including those associated with neurodegeneration. Using a well-characterized rodent model of remote neuronal degeneration, Oddi et al. (J Mol Med 2012, in press, DOI                             10.1007/s00109-012-0884-1                                                     ) have demonstrated that targeting CB(2) cannabinoid receptors may represent a promising novel approach to attenuate this pathological process. This editorial discusses the clinical significance of these interesting observations and the mechanisms of the possible interplay of CB(2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration.
authors.forename: Pál
authors.initials: P
authors.lastname: Pacher
authors.forename: Ken
authors.initials: K
authors.lastname: Mackie
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000473:pathology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics*; D043885:Receptor, Cannabinoid, CB2 / Q000378:metabolism*
chemical_list: D018696:Neuroprotective Agents; D043885:Receptor, Cannabinoid, CB2; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat