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Endocannabinoid Hydrolysis Generates Brain Prostaglandins That Promote Neuroinflammation
Science (2011)
Abstract
Phospholipase A2(PLA2) enzymes are considered the primary source of arachidonic acid for cyclooxygenase (COX)–mediated biosynthesis of prostaglandins. Here, we show that a distinct pathway exists in brain, where monoacylglycerol lipase (MAGL) hydrolyzes the endocannabinoid 2-arachidonoylglycerol to generate a major arachidonate precursor pool for neuroinflammatory prostaglandins. MAGL-disrupted animals show neuroprotection in a parkinsonian mouse model. These animals are spared the hemorrhaging caused by COX inhibitors in the gut, where prostaglandins are instead regulated by cytosolic PLA2. These findings identify MAGL as a distinct metabolic node that couples endocannabinoid to prostaglandin signaling networks in the nervous system and suggest that inhibition of this enzyme may be a new and potentially safer way to suppress the proinflammatory cascades that underlie neurodegenerative disorders.
Disciplines
Publication Date
November 11, 2011
Publisher Statement
For a complete list of authors, please refer to the article.
Citation Information
"Endocannabinoid Hydrolysis Generates Brain Prostaglandins That Promote Neuroinflammation" Science Vol. 334 Iss. 6057 (2011)
Available at: http://works.bepress.com/brad_morrison/6/