The endocannabinoid system as a target for the treatment of neuronal damage.
BACKGROUND
Cannabinoids have been proposed as clinically promising neuroprotective molecules, based on their capability to normalize glutamate homeostasis, reducing excitotoxicity, to inhibit calcium influx, lowering intracellular levels and the subsequent activation of calcium-dependent destructive pathways, and to reduce the generation of reactive oxygen intermediates or to limit their toxicity, decreasing oxidative injury. Cannabinoids are also able to decrease local inflammatory events by acting on glial processes that regulate neuronal survival, and to restore blood supply by reducing vasocontriction produced by several endothelium-derived factors.


METHODS
Current literature supporting these neuroprotective effects, particularly evidence generated during the last ten years, concentrating on targets within the cannabinoid signaling system that facilitate these effects. Acute or chronic neurodegenerative disorders where cannabinoids have shown neuroprotective effect.


RESULTS
Most of the information reviewed here relates to preclinical studies. However, these molecules may progress from the present preclinical evidence to clinical applications.


CONCLUSIONS
Treatment of neurodegenerative disorders is a challenge for neuroscientists and neurologists. Unhappily, the efficacy of available medicines is still poor and there is an urgent need for novel neuroprotective agents. Cannabinoids can serve this purpose given their recognized antiexcitotoxic, antioxidant and anti-inflammatory properties.
Departamento de Bioquímica y Biología Molecular III, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria s/n, 28040-Madrid, Spain. jjfr@med.ucm.es
Javier
J
Fernández-Ruiz
Concepción
C
García
Onintza
O
Sagredo
María
M
Gómez-Ruiz
Eva
E
de Lago
D000818:Animals; D063385:Cannabinoid Receptor Modulators / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D063388:Endocannabinoids; D006801:Humans; D009422:Nervous System Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D043882:Receptors, Cannabinoid / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D018696:Neuroprotective Agents; D043882:Receptors, Cannabinoid