Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.
Monoglyceride lipase as a drug target: At the crossroads of arachidonic acid metabolism and endocannabinoid signaling.
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DOI：
10.1016/j.pharmthera.2017.02.033
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发表时间：
2017-07
影响因子：
13.5
通讯作者：
Taschler U
中科院分区：
文献类型：
--
作者：
Grabner GF;Zimmermann R;Schicho R;Taschler U
单甘油酯（mg）是一种由磷酸脂和中性脂降解产生的短命的中间脂类，而单甘油酯脂肪酶（MGL），也被称为单酰基甘油脂肪酶（MAGL），是催化mg水解成甘油和脂肪酸的主要酶。这种独特的功能使MGL能够调节许多生理和病理生理过程，因为mg和脂肪酸都可以作为信号脂质或其前体。作为信号脂质最突出的MG种是2-花生四烯醇甘油（2-AG），它是体内最丰富的内源性大麻素受体激动剂。重要的是，最近的观察表明，2-AG是花生四烯酸的重要来源，花生四烯酸是前列腺素和其他炎症介质的前体。因此，mgl介导的2-AG降解通过大麻素受体依赖和独立的机制影响脂质信号传导。最近的遗传和药理学研究为MGL在病理生理过程中的作用提供了重要的见解，该酶现在被认为是包括癌症、神经退行性疾病和炎症性疾病在内的许多疾病的有希望的药物靶点。本文综述了MG （2-AG）代谢的基础知识，并对MGL的治疗潜力进行了综述。
Monoglyerides (MGs) are short-lived, intermediary lipids deriving from the degradation of phospho- and neutral lipids, and monoglyceride lipase (MGL), also designated as monoacylglycerol lipase (MAGL), is the major enzyme catalyzing the hydrolysis of MGs into glycerol and fatty acids. This distinct function enables MGL to regulate a number of physiological and pathophysiological processes since both MGs and fatty acids can act as signaling lipids or precursors thereof. The most prominent MG species acting as signaling lipid is 2-arachidonoyl glycerol (2-AG) which is the most abundant endogenous agonist of cannabinoid receptors in the body. Importantly, recent observations demonstrate that 2-AG represents a quantitatively important source for arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. Accordingly, MGL-mediated 2-AG degradation affects lipid signaling by cannabinoid receptor-dependent and independent mechanisms. Recent genetic and pharmacological studies gave important insights into MGL’s role in (patho-)physiological processes, and the enzyme is now considered as a promising drug target for a number of disorders including cancer, neurodegenerative and inflammatory diseases. This review summarizes the basics of MG (2-AG) metabolism and provides an overview on the therapeutic potential of MGL.