Compound 4f, a novel brain-penetrant reversible monoacylglycerol inhibitor, ameliorates neuroinflammation, neuronal cell loss, and cognitive impairment in mice with kainic acid-induced neurodegeneration.

ABSTRACT: Neuroinflammation, a hallmark of neurodegenerative diseases, is associated with neuronal cell loss and cognitive dysfunction. Monoacylglycerol lipase (MAGL) is involved in neuroinflammation in the brain via the degradation of endocannabinoid 2-arachidonoylglycerol to arachidonic acid, a precursor of some eicosanoids; therefore, MAGL inhibitors are expected to have anti-inflammatory effects. We recently developed a reversible, selective, central nervous system penetrant, and orally available MAGL inhibitor, compound 4f. Compound 4f (1 mg/kg) robustly increased 2-arachidonoylglycerol levels and decreased arachidonic acid levels in the mouse brain. To examine whether compound 4f can suppress neuroinflammation and neuronal cell loss, kainic acid (KA)-injected mice were used as a neuroinflammat

SUBMITTER: Arimura N 

PROVIDER: S-EPMC11581214 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature