A Second Fatty Acid Amide Hydrolase with Variable Distribution among Placental Mammals

Wei, BinQing; Mikkelsen, Tarjei S.; McKinney, Michele K.; Lander, Eric S.; Cravatt, Benjamin F.

doi:10.1074/jbc.m606646200

Cited by 312 publications

(291 citation statements)

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“…The latter compound is next cleaved by a specific N-acylphosphatidylethanolamine (NAPE)-specific phospholipase D, which has been characterized in detail [8]. However, the degradation of AEA to AA and ethanolamine is mainly due to 2 fatty acid amide hydrolases (FAAH and FAAH-2) [9,10]. When FAAH and FAAH-2 are inhibited, N-acylethanolaminehydrolyzing acid amidase cleaves AEA in an alternate route [11,12].…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Endocannabinoid Signaling in Autism

et al. 2015

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Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the Bendocannabinoid (eCB) system^, a rather complex ensemble of lipid signals (Bendocannabinoids^), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.Key Words Autism spectrum disorder . endocannabinoid system . fragile X syndrome . metabolic regulation . reward system The Endocannabinoid SystemTwenty-five years after the cloning and expression of a complementary DNA that encoded a G protein-coupled receptor, named type-1 cannabinoid (CB 1 ) receptor [1], there is a good deal of information on the main components of the so-called Bendocannabinoid (eCB) system^, as well as on its role in controlling cannabinergic signaling in human health and disease [2][3][4]. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most active eCBs as yet identified, although this family of bioactive lipids includes other arachidonic acid (AA) derivatives with cannabimimetic properties (i.e., noladin ether, virodhamine, N-arachidonoyldopamine, to name but a few). The classical dogma that eCBs are synthesized and released Bon demand^upon (patho)physiological stimuli has been recently revisited on the basis of unexpected evidence for intracellular reservoirs and transporters of eCBs. These new entities have been shown to drive intracellular trafficking of eCBs, adding a new dimension to the regulation of their biological activity [5]. To date, several metabolic routes have B. Chakrabarti, A. Persico and N. Battista are equal first authors.

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Section: The Endocannabinoid Systemmentioning

confidence: 99%

Endocannabinoid Signaling in Autism

et al. 2015

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“…COS-7 cells do not express FAAH and are therefore suitable for FAAH re-localization studies (34). Rat FAAH was fused to eGFP at its C terminus (Fig.…”

Section: Aea Cellular Uptake Is Rapid and Independent Of Subcellular mentioning

confidence: 99%

Identification of intracellular carriers for the endocannabinoid anandamide

Kaczocha¹,

Glaser

Deutsch³

2009

Proc. Natl. Acad. Sci. U.S.A.

311

332

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The endocannabinoid anandamide (arachidonoyl ethanolamide, AEA) is an uncharged neuromodulatory lipid that, similar to many neurotransmitters, is inactivated through its cellular uptake and subsequent catabolism. AEA is hydrolyzed by fatty acid amide hydrolase (FAAH), an enzyme localized on the endoplasmic reticulum. In contrast to most neuromodulators, the hydrophilic cytosol poses a diffusional barrier for the efficient delivery of AEA to its site of catabolism. Therefore, AEA likely traverses the cytosol with the assistance of an intracellular carrier that increases its solubility and rate of diffusion. To study this process, AEA uptake and hydrolysis were examined in COS-7 cells expressing FAAH restricted to the endoplasmic reticulum, mitochondria, or the Golgi apparatus. AEA hydrolysis was detectable at the earliest measurable time point (

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“…AEA is also hydrolyzed by other enzymes such as FAAH-2, a second FAAH isoform [10], and N-acylethanolaminehydrolyzing acid amidase (NAAA) [11]. FAAH has a broad substrate selectivity, and it has been well characterized both pharmacologically and biochemically.…”

Section: Introductionmentioning

confidence: 99%