期刊
EXPERIMENTAL NEUROLOGY
卷 224, 期 1, 页码 48-55出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2010.03.022
关键词
Oleoylethanolamide; Neuroprotection; PPAR alpha; Ischemia; N-acylethanolamine; Stearoylethanolamide; N-oleoylethanolamine; Ceramidase; N-palmitoylethanolamine; Memory; Neurosteroids; Potassium channels
资金
- Novonordisk Foundation
- Danish Ministry of Science, Technology and Innovation
Acylethanolamides are formed in the brain on demand from membrane phospholipids called N-acylated phosphatidylethanolamines. The acylethanolamides are signaling molecules of lipid nature, and this lipofilicity suggests an autocrine function. The acylethanolamides include palmitoylethanolamide (PEA), oleoylethanolamide (OEA), stearoylethanolamide (SEA), and several other quantitative minor species including anandamide (= arachidonoylethanolamide). PEA and OEA can activate several different receptors and inhibit some ion channels, e.g., PPAR alpha, vanilloid receptor. K channels (Kv4.3, Kv1.5), and OEA can activate GPR119 and inhibit ceramidases. Targets for SEA are less clear, but it has some cannabimimetic actions in rats in vivo. All acylethanolamides accumulate during neuronal injury, and injected IDEA has neuroprotective effects, and PEA has anti-inflammatory effects as studied in the peripheral system. Several of the pharmacological effects seem to be mediated via activation of PPARa. Recently, injected OEA has been found to consolidate memories in rats. Inhibitors of the acylethanolamide-degrading enzyme FAAH can increase levels of all acylethanolamides including annandamide, and some of the pharmacological effects caused by these inhibitors may be explained by increased cerebral levels of OEA and PEA, e.g., suppression of nicotine-induced activation of dopamine neurons. Furthermore, through activation of PPAR alpha, OEA and PEA may stimulate neurosteroid synthesis, thereby modulating several biological functions mediated by GABA(A) receptors. The existence of acylethanolamides in the mammalian brain has been known for decades, but it is first within the last few years that the putative biological functions of the three most abundant acylethanolamides species are starting to emerge. (C) 2010 Elsevier Inc. All rights reserved.
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