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CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Biosynthetic Pathways of Bioactive N-Acylethanolamines in Brain

Author(s): Kazuhito Tsuboi, Natsuki Ikematsu, Toru Uyama, Dale G. Deutsch, Akira Tokumura and Natsuo Ueda

Volume 12, Issue 1, 2013

Page: [7 - 16] Pages: 10

DOI: 10.2174/1871527311312010005

Price: $65

Abstract

Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators generally referred to as Nacylethanolamines (NAEs). NAEs include anti-inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide, and the endocannabinoid anandamide. Since the endogenous levels of NAEs are principally regulated by enzymes responsible for their biosynthesis and degradation, these enzymes are expected as targets for the development of therapeutic agents. Thus, a better understanding of these enzymes is indispensable. The classic “N-acylationphosphodiesterase pathway” for NAE biosynthesis is composed of two steps; the formation of Nacylphosphatidylethanolamine (NAPE) by N-acyltransferase and the release of NAE from NAPE by NAPE-hydrolyzing phospholipase D (NAPE-PLD). However, recent studies, including the analysis of NAPE-PLD-deficient (NAPE-PLD-/-) mice, revealed the presence of NAPE-PLD-independent multi-step pathways to form NAEs from NAPE in animal tissues. Our recent studies using NAPE-PLD-/- mice also suggest that NAE is formed not only from NAPE, but also from Nacylated plasmalogen-type ethanolamine phospholipid (N-acyl-plasmenylethanolamine) through both NAPE-PLDdependent and -independent pathways. Here, we present recent findings on NAE biosynthetic pathways mainly occurring in the brain.

Keywords: N-Acylethanolamine, anandamide, biosynthesis, NAPE-PLD, oleoylethanolamide, palmitoylethanolamide, phospholipid, plasmalogen


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