title: Prospects for cannabinoid therapies in basal ganglia disorders.
abstract: Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ(9) -tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxidative injury is a prominent cytotoxic mechanism. This effect could be exerted, at least in part, through mechanisms independent of CB(1) and CB(2) receptors and involving the control of endogenous antioxidant defences. On the other hand, the activation of CB(2) receptors leads to a slower progression of neurodegeneration in both disorders. This effect would be exerted by limiting the toxicity of microglial cells for neurons and, in particular, by reducing the generation of proinflammatory factors. It is important to mention that CB(2) receptors have been identified in the healthy brain, mainly in glial elements and, to a lesser extent, in certain subpopulations of neurons, and that they are dramatically up-regulated in response to damaging stimuli, which supports the idea that the cannabinoid system behaves as an endogenous neuroprotective system. This CB(2) receptor up-regulation has been found in many neurodegenerative disorders including HD and PD, which supports the beneficial effects found for CB(2) receptor agonists in both disorders. In conclusion, the evidence reported so far supports that those cannabinoids having antioxidant properties and/or capability to activate CB(2) receptors may represent promising therapeutic agents in HD and PD, thus deserving a prompt clinical evaluation.
authors.affiliation: Departamento de Bioquímica y Biología Molecular III, Instituto Universitario de Investigación en Neuroquímica, Facultad de Medicina, Universidad Complutense, Madrid, Spain. jjfr@med.ucm.es
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
authors.forename: Miguel
authors.initials: M
authors.lastname: Moreno-Martet
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez-Cueto
authors.forename: Cristina
authors.initials: C
authors.lastname: Palomo-Garo
authors.forename: María
authors.initials: M
authors.lastname: Gómez-Cañas
authors.forename: Sara
authors.initials: S
authors.lastname: Valdeolivas
authors.forename: Carmen
authors.initials: C
authors.lastname: Guaza
authors.forename: Julián
authors.initials: J
authors.lastname: Romero
authors.forename: Manuel
authors.initials: M
authors.lastname: Guzmán
authors.forename: Raphael
authors.initials: R
authors.lastname: Mechoulam
authors.forename: José A
authors.initials: JA
authors.lastname: Ramos
mesh_terms: D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D001480:Basal Ganglia Diseases / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2