Endocannabinoid 2-arachidonoylglycerol protects neurons against β-amyloid insults

摘要: While endocannabinoid modulation of both GABAergic and glutamatergic synaptic transmission plasticity has been extensively investigated, our understanding the role endocannabinoids in protecting neurons from harmful insults remains limited. 2-Arachidonoylglycerol (2-AG), most abundant endogenous ligand a full agonist for cannabinoid receptors, exhibits anti-inflammatory neuroprotective effects via CB1 receptor (CB1R)-mediated mechanism. However, it is still not clear whether 2-AG also able to protect β-amyloid (Aβ)-induced neurodegeneration. Here, we demonstrate that exogenous application significantly protected hippocampal culture against Aβ-induced neurodegeneration apoptosis. This effect was blocked by SR141716 (SR-1), selective CB1R antagonist, but SR144528 (SR-2), CB2R or capsazepine (CAP), transient potential cation channels, subfamily V, member 1 (TRPV1) antagonist. To determine capable Aβ insults, were treated with URB602 JZL184, inhibitors monoacylglycerol lipase (MAGL), enzyme hydrolyzing 2-AG. MAGL inhibition elevates levels reduced The 2-AG-produced appear be mediated CB1R-dependent suppression extracellular signal-regulated kinases 2 (ERK1/2) nuclear factor-κB (NF-κB) phosphorylation cyclooxygenase-2 (COX-2) expression. Our results suggest elevation inhibiting its hydrolysis as novel efficacious therapeutic approach preventing, ameliorating treating Alzheimer's disease.