Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China; Targeted Tracer Research and Development Laboratory, Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Eur J Med Chem. 2020 Jul 15;198:112353. doi: 10.1016/j.ejmech.2020.112353. Epub 2020 Apr 25.
α/β-Hydrolase domain 6 (ABHD6) is a transmembrane serine hydrolase that hydrolyzes monoacylglycerol (MAG) lipids, particularly the endogenous cannabinoid 2-arachidonoylglycerol (2-AG), in both central and peripheral tissues. ABHD6 and its substrates have been shown to be involved in the modulation of various (patho)physiological processes, including neurotransmission, inflammation, insulin secretion, adipose browning, food intake, autoimmune disorders, as well as neurological and metabolic diseases, making this enzyme a promising therapeutic target to treat several diseases. This review will focus on the molecular mechanism, biological functions and pathological roles of ABHD6, as well as recent efforts to develop ABHD6 inhibitors, providing a strong basis for the development of small molecules by targeting ABHD6 to treat diverse diseases.
α/β-水解酶结构域蛋白 6（ABHD6）是一种跨膜丝氨酸水解酶，能够水解单酰基甘油（MAG）脂质，尤其是内源性大麻素 2-花生四烯酰甘油（2-AG），在中枢和外周组织中均有此作用。ABHD6 及其底物参与了多种（病理）生理过程的调节，包括神经传递、炎症、胰岛素分泌、脂肪褐变、摄食、自身免疫性疾病以及神经和代谢性疾病，这使得该酶成为治疗多种疾病的有前途的治疗靶点。本综述将重点介绍 ABHD6 的分子机制、生物学功能和病理作用，以及最近开发 ABHD6 抑制剂的努力，为针对 ABHD6 开发小分子以治疗多种疾病提供了坚实的基础。
