Abstract | AIMS: MAIN METHODS: This proposition is supported by data from numerous in vitro and in vivo experiments establishing metabolic and pharmacological contexts for the neuroprotective role of the endogenous cannabinoid (" endocannabinoid") system and selective FAAH inhibitors. KEY FINDINGS: The systems biology of endocannabinoid signaling involves two main cannabinoid receptors, the principal endocannabinoid lipid mediators N-arachidonoylethanolamine (" anandamide") (AEA) and 2-arachidonoyl glycerol (2-AG), related metabolites, and the proteins involved in endocannabinoid biosynthesis, biotransformation, and transit. The endocannabinoid system is capable of activating distinct signaling pathways on-demand in response to pathogenic events or stimuli, thereby enhancing cell survival and promoting tissue repair. Accumulating data suggest that endocannabinoid system modulation at discrete targets is a promising pharmacotherapeutic strategy for treating various medical conditions. In particular, neuronal injury activates cannabinoid signaling in the central nervous system as an intrinsic neuroprotective response. Indirect potentiation of this salutary response through pharmacological inhibition of FAAH, an endocannabinoid-deactivating enzyme, and consequent activation of signaling pathways downstream from cannabinoid receptors have been shown to promote neuronal maintenance and function. SIGNIFICANCE: This therapeutic modality has the potential to offer site- and event-specific neuroprotection under conditions where endocannabinoids are being produced as part of a physiological protective mechanism. In contrast, direct application of cannabinoid receptor agonists to the central nervous system may activate CB receptors indiscriminately and invite unwanted psychotrophic effects.
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Authors | Jeannie Hwang, Crista Adamson, David Butler, David R Janero, Alexandros Makriyannis, Ben A Bahr |
Journal | Life sciences
(Life Sci)
Vol. 86
Issue 15-16
Pg. 615-23
(Apr 10 2010)
ISSN: 1879-0631 [Electronic] Netherlands |
PMID | 19527737
(Publication Type: Journal Article, Review)
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Copyright | Copyright 2009 Elsevier Inc. All rights reserved. |
Chemical References |
- Cannabinoid Receptor Modulators
- Endocannabinoids
- Neuroprotective Agents
- Amidohydrolases
- fatty-acid amide hydrolase
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Topics |
- Amidohydrolases
(antagonists & inhibitors)
- Animals
- Cannabinoid Receptor Modulators
(metabolism)
- Drug Delivery Systems
- Endocannabinoids
- Humans
- Nervous System Diseases
(drug therapy, physiopathology)
- Neurodegenerative Diseases
(drug therapy, physiopathology)
- Neuroprotective Agents
(pharmacology, therapeutic use)
- Signal Transduction
(drug effects)
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