title: The endocannabinoid system in neurodegeneration.
abstract: Endocannabinoids are bioactive lipids, that comprise amides, esters and ethers of long chain polyunsaturated fatty acids. Anandamide (N-arachidonoylethanolamine; AEA) and 2-arachidonoylglycerol (2-AG) are the best studied endocannabinoids, and act as agonists of cannabinoid receptors. Thus, AEA and 2-AG mimic several pharmacological effects of the exogenous cannabinoid delta9-tetrahydrocannabinol, the psychoactive principle of hashish and marijuana. It is known that the activity of endocannabinoids at their receptors is limited by cellular uptake through specific membrane transporters, followed by intracellular degradation by a fatty acid amide hydrolase (for AEA and partly 2-AG) or by a monoacylglycerol lipase (for 2-AG). Together with AEA, 2-AG and congeners, the proteins that bind, transport and metabolize these lipids form the "endocannabinoid system". This new system will be briefly presented in this review, in order to put in a better perspective the role of the endocannabinoid pathway in neurodegenerative disorders, like Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, the potential exploitation of antagonists of endocannabinoid receptors, or of inhibitors of endocannabinoid metabolism, as next-generation therapeutics will be discussed.
authors.affiliation: Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
authors.forename: Natalia
authors.initials: N
authors.lastname: Battista
authors.forename: Filomena
authors.initials: F
authors.lastname: Fezza
authors.forename: Alessandro
authors.initials: A
authors.lastname: Finazzi-Agrò
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000502:physiology*; D002490:Central Nervous System / Q000378:metabolism; D063388:Endocannabinoids; D005989:Glycerides / Q000502:physiology; D006801:Humans; D006816:Huntington Disease / Q000503:physiopathology; D009103:Multiple Sclerosis / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000503:physiopathology*; D010300:Parkinson Disease / Q000503:physiopathology; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid / Q000502:physiology*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D043882:Receptors, Cannabinoid; C094503:glyceryl 2-arachidonate; C078814:anandamide