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Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective therapeutic modality.
Life Sci 2010; 86(15-16):615-23LS

Abstract

AIMS

This review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic brain injury; Alzheimer's, Huntington's, and Parkinson's diseases; and stroke.

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.

Authors+Show Affiliations

Department of Pharmaceutical Sciences and the Neurosciences Program, University of Connecticut, Storrs, Connecticut, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

19527737

Citation

Hwang, Jeannie, et al. "Enhancement of Endocannabinoid Signaling By Fatty Acid Amide Hydrolase Inhibition: a Neuroprotective Therapeutic Modality." Life Sciences, vol. 86, no. 15-16, 2010, pp. 615-23.
Hwang J, Adamson C, Butler D, et al. Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective therapeutic modality. Life Sci. 2010;86(15-16):615-23.
Hwang, J., Adamson, C., Butler, D., Janero, D. R., Makriyannis, A., & Bahr, B. A. (2010). Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective therapeutic modality. Life Sciences, 86(15-16), pp. 615-23. doi:10.1016/j.lfs.2009.06.003.
Hwang J, et al. Enhancement of Endocannabinoid Signaling By Fatty Acid Amide Hydrolase Inhibition: a Neuroprotective Therapeutic Modality. Life Sci. 2010 Apr 10;86(15-16):615-23. PubMed PMID: 19527737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective therapeutic modality. AU - Hwang,Jeannie, AU - Adamson,Crista, AU - Butler,David, AU - Janero,David R, AU - Makriyannis,Alexandros, AU - Bahr,Ben A, Y1 - 2009/06/13/ PY - 2009/03/03/received PY - 2009/05/28/revised PY - 2009/06/03/accepted PY - 2009/6/17/entrez PY - 2009/6/17/pubmed PY - 2010/4/16/medline SP - 615 EP - 23 JF - Life sciences JO - Life Sci. VL - 86 IS - 15-16 N2 - AIMS: This review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic brain injury; Alzheimer's, Huntington's, and Parkinson's diseases; and stroke. 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/19527737/Enhancement_of_endocannabinoid_signaling_by_fatty_acid_amide_hydrolase_inhibition:_a_neuroprotective_therapeutic_modality_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(09)00262-8 DB - PRIME DP - Unbound Medicine ER -