title: Inhibitors of diacylglycerol lipases in neurodegenerative and metabolic disorders.
abstract: 2-Arachidonoylglycerol (2-AG) is an endocannabinoid that activates the cannabinoid receptors type 1 and 2. It also serves as an important lipid precursor for the eicosanoid signaling pathway. Consequently, 2-AG is involved in many physiological functions, including anxiety, food intake, inflammation, memory, pain sensation and neurotransmission. Diacylglycerol lipases (DAGLs) are the main biosynthetic enzymes for 2-AG and their role in several pathophysiological conditions is currently under investigation. In this Digest we review all DAGL inhibitors reported to date and their effects in preclinical models of neurodegeneration and metabolic disorders.
authors.affiliation: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, Netherlands.
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Janssen
authors.affiliation: Department of Molecular Physiology, Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, Netherlands. Electronic address: m.van.der.stelt@chem.leidenuniv.nl.
authors.forename: Mario
authors.initials: M
authors.lastname: van der Stelt
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000627:therapeutic use; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D008071:Lipoprotein Lipase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D011485:Protein Binding; D043882:Receptors, Cannabinoid / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D005989:Glycerides; D043882:Receptors, Cannabinoid; D054852:Small Molecule Libraries; C094503:glyceryl 2-arachidonate; D008071:Lipoprotein Lipase
keywords: 2-Arachidonoylglycerol; Diacylglycerol lipases; Drug development; Metabolic syndrome; Neurodegenerative diseases; Neuroinflammation; Obesity