Diacylglycerol lipase alpha (DAGLA) (DAGLA)

Diacylglycerol lipase alpha (DAGLα) is a critical enzyme responsible for the biosynthesis of 2-arachidonoylglycerol (2-AG), which is the most prevalent endocannabinoid in the mammalian central nervous system (UniProt Q9Y4D2). As a sn-1 specific serine hydrolase, DAGLα converts diacylglycerol into 2-AG, a lipid signaling molecule that acts as a retrograde messenger to modulate synaptic plasticity and neurotransmitter release via cannabinoid receptors (PubMed: 12620237). Beyond its role in the adult brain, DAGLα is essential for axonal growth and guidance during neural development and continues to regulate adult neurogenesis (PubMed: 27325658). Pathologically, altered DAGLα activity is linked to neurodegenerative conditions such as Parkinson's and Alzheimer's diseases, as well as chronic pain, neuroinflammation, and metabolic syndromes (PubMed: 28214380). Pharmacological inhibition of DAGLα is being investigated as a strategy to reduce 2-AG-mediated signaling in these contexts, although such interventions must be balanced against potential side effects like anxiety or depression due to the enzyme's role in mood regulation (PubMed: 24910363). While several potent and selective small-molecule inhibitors like DO34 and KT109 have been developed for research, clinical applications remain in the early stages of exploration (PubMed: 30103318).

Other names

DAGLADGL-alphasn1-specific diacylglycerol lipase alphaNeural stem cell-derived dendrite regulatorNSDHL2

Inhibition of diacylglycerol lipase activity to reduce the production of 2-arachidonoylglycerol (2-AG) and its subsequent signaling through cannabinoid receptors (PubMed: 27325658).