Dampening neuroinflammation



Figure 1. Connecting cannabinoid and prostaglandin pathways. A team led by researchers from The Scripps Research Institute and the University of California, Berkeley have shown that monoacylglycerol lipase (MAGL), which controls levels of a pain-reducing metabolite in the brain, also regulates neuroinflammation. Thus, blocking MAGL could provide a therapeutic benefit in neurodegenerative disorders characterized by neuroinflammation.

Previous work from Scripps had shown that in mice, a small molecule inhibitor of MAGL [a] increased the levels of 2-arachidonoylglycerol (2-AG) in the brain, which acted through the cannabinoid receptors to decrease pain [b]. The team has now shown that in a mouse model of neuroinflammation, inhibiting MAGL lowers the production of arachidonic acid to decrease levels of inflammatory prostaglandins and blunt inflammation in the brain [c].

In a mouse model of neurotoxin-induced Parkinson's disease (PD), a MAGL inhibitor reduced neuroinflammation and dopaminergic neurodegeneration compared with vehicle.