The seek of neuroprotection: introducing cannabinoids.
The cannabinoid system is constituted by some endogenous ligands (endocannabinoids), usually arachydonic acid derivatives, and their specific receptors. The endogenous cannabinoid system (ECS) is involved in the control of synaptic transmission, modulating memory, motivation, movement, nociception, appetite and thermoregulation. ECS also exert extraneural effects, mainly immunomodulation and vasodilation. Two cannabinoid receptors have been cloned so far: CB(1) receptors are expressed in the central nervous system (CNS) but can also be found in glial cells and in peripheral tissues; CB(1) receptors are Gi/o protein coupled receptors that modulate the activity of several plasma membrane proteins and intracellular signaling pathways. CB(2) receptors are also Gi/o protein-coupled receptors; although it is accepted that CB(2) receptors are not expressed in forebrain neurons, they have been described in activated glia. Some of the cannabinoids activate other receptors, for instance vanilloid receptors (TRPV1). Lately, the ECS is emerging as a natural system of neuroprotection. This consideration is based on some properties of cannabinoids as their vasodilatory effect, the inhibition of the release of excitotoxic amino acids and cytokines, and the modulation of oxidative stress and toxic production of nitric oxide. Such effects have been demonstrated in adult and newborn animal models of acute and chronic neurodegenerative conditions, and postulate cannabinoids as valuable neuroprotective agents. Patents related to cannabinoid receptors are also discussed.
Martínez-Orgado
Jose
J
Area de Pediatría y Neonatología, Fundación Hospital Alcorcón; Budapest, 1; 28922-Alcorcón Madrid, Spain. jamartinezo@fhalcorcon.es
Fernández-López
David
D
Lizasoain
Ignacio
I
Romero
Julián
J
D000818:Animals; D001921:Brain / Q000254:growth & development; D002186:Cannabinoids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000502:physiology
D002186:Cannabinoids; D018696:Neuroprotective Agents; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2