title: Cannabinoids and neuroprotection in basal ganglia disorders.
abstract: Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity, calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders including Parkinson's disease and Huntington's chorea, two chronic diseases that are originated as a consequence of the degeneration of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases have been still scarcely explored at the clinical level for a possible application of cannabinoids to delay the progressive degeneration of the basal ganglia. However, the preclinical evidence seems to be solid and promising. There are two key mechanisms involved in the neuroprotection by cannabinoids in experimental models of these two disorders: first, a cannabinoid receptor-independent mechanism aimed at producing a decrease in the oxidative injury and second, an induction/upregulation of cannabinoid CB2 receptors, mainly in reactive microglia, that is capable to regulate the influence of these glial cells on neuronal homeostasis. Considering the relevance of these preclinical data and the lack of efficient neuroprotective strategies in both disorders, we urge the development of further studies that allow that the promising expectatives generated for these molecules progress from the present preclinical evidence till a real clinical application.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina III, Universidad Complutense, Ciudad Universitaria s/n, 28040 Madrid, Spain.
authors.forename: Onintza
authors.initials: O
authors.lastname: Sagredo
authors.forename: Moisés
authors.initials: M
authors.lastname: García-Arencibia
authors.forename: Eva
authors.initials: E
authors.lastname: de Lago
authors.forename: Simone
authors.initials: S
authors.lastname: Finetti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Decio
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
mesh_terms: D000818:Animals; D001480:Basal Ganglia Diseases / Q000188:drug therapy*; D002186:Cannabinoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy
chemical_list: D002186:Cannabinoids; D018696:Neuroprotective Agents