Monoacylglycerol lipase (MAGL) has been characterized as the main enzyme responsible for the inactivation of the most abundant brain endocannabinoid, 2-arachidonoylglycerol (2-AG). Besides this role, MAGL has progressively acquired a growing importance as an integrative metabolic hub that controls not only the in vivo levels of 2-AG but also of other monoacylglycerides and, indirectly, the levels of free fatty acids derived from their hydrolysis as well as other lipids with pro-inflammatory or pro-tumorigenic effects, coming from the further metabolism of fatty acids. All these functions have only started to be elucidated in the last years due to the progress made in the knowledge of the structure of MAGL and in the development of genetic and chemical tools. In this review we report the advances made in the field with a special focus on the last decade and how MAGL has become a promising therapeutic target for the treatment of several diseases that currently lack appropriate therapies.
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http://dx.doi.org/10.1016/j.bcp.2018.07.036 | DOI Listing |
Eur J Med Chem
January 2025
Department of Radiology and Imaging Sciences, Emory University, 1364 Clifton Road, Atlanta, GA, 30322, United States. Electronic address:
Monoacylglycerol lipase (MAGL) is a 33 kDa cytosolic serine hydrolase that is widely distributed in the central nervous system and peripheral tissues. MAGL hydrolyzes monoacylglycerols into fatty acids and glycerol, playing a crucial role in endocannabinoid degradation. Inhibition of MAGL in the brain elevates levels of 2-arachidonoylglycerol and leads to decreased pro-inflammatory prostaglandin and thromboxane production.
View Article and Find Full Text PDFNutrients
December 2024
Department of Neurosciences, Faculty of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Leioa, Spain.
: Omega-3 long-chain polyunsaturated fatty acids (PUFAs) support brain cell membrane integrity and help mitigate synaptic plasticity deficits. The endocannabinoid system (ECS) is integral to synaptic plasticity and regulates various brain functions. While PUFAs influence the ECS, the effects of omega-3 on the ECS, cognition, and behavior in a healthy brain remain unclear.
View Article and Find Full Text PDFCurr Top Behav Neurosci
January 2025
Pharma Research and Early Development (pRED), Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
Cannabis sativa has been used therapeutically since early civilizations, with key cannabinoids Δ-tetrahydrocannabinol (THC) 3.1 and cannabidiol characterized in the 1960s, leading to the discovery of cannabinoid receptors type 1 (CBR) and type 2 (CBR) and the endocannabinoid system (ECS) in the 1990s. The ECS, involving endogenous ligands like 2-arachidonoylglycerol (2-AG) 1.
View Article and Find Full Text PDFBMC Plant Biol
December 2024
College of Advanced Agricultural Sciences, Zhejiang A & F University, Hangzhou, 311300, China.
Background: Monoacylglycerol lipase (MAGL) belongs to the serine hydrolase family; it catalyzes MAG to produce glycerol and free fatty acids (FFAs), which is the final step in triacylglycerol (TAG) hydrolysis. The effects of MAGL on comprehensive lipid metabolism and plant growth and development have not been elucidated, especially in Arachis hypogaea, an important oil crop.
Results: Herein, AhMAGL3b encoding a protein with both hydrolase and acyltransferase regions, a member of MAGL gene family, was cloned and overexpressed in Arabidopsis thaliana.
Mol Neurobiol
December 2024
Department of Emergency Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.
Astrocytes are abundant glial cells in the central nervous system (CNS) that play important roles in brain injury following cardiac arrest (CA). Following brain ischemia, astrocytes trigger endogenous neuroprotective mechanisms, such as fatty acid transport. Lipid droplets (LDs) are cellular structures involved in neutral lipid storage and play essential roles in many biological processes.
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