Monoacylglycerol lipase (MAGL) (MAGL)

Monoacylglycerol lipase (MAGL) is a key serine hydrolase responsible for the biological inactivation of 2-arachidonoylglycerol (2-AG), the most prevalent endocannabinoid in the mammalian nervous system (UniProt Q99685). By catalyzing the hydrolysis of 2-AG into arachidonic acid and glycerol, MAGL serves as a critical metabolic hub that links endocannabinoid signaling to the production of pro-inflammatory prostaglandins (PubMed: 20337383). The human isoform of the enzyme (hMAGL) contains several reactive cysteine residues, most notably Cys115, which is situated near the entrance of the catalytic pocket and serves as a site for covalent modification by various electrophilic compounds (PubMed: 19029917). Research has identified isoflavones, such as daidzein and its synthetic derivatives, as potential scaffolds for developing inhibitors that can form stable conjugate linkages with these regulatory cysteines (PubMed: 22616033). Therapeutic modulation of MAGL is considered a promising approach for treating conditions such as chronic pain, neuroinflammation, and cancer, as it allows for the elevation of endocannabinoid tone without the global activation of cannabinoid receptors associated with direct agonists.

Other names

MGLLMGLMonoacylglyceride lipaseHU-K5Lysophospholipase-likehMAGLhMGL

Inhibition of Monoacylglycerol lipase (MAGL) prevents the breakdown of 2-arachidonoylglycerol (2-AG), leading to increased endocannabinoid signaling at CB1 and CB2 receptors and reduced production of pro-inflammatory prostaglandins.