Journal
SCIENCE
Volume 334, Issue 6057, Pages 809-813Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1209200
Keywords
-
Categories
Funding
- NIH [DA017259, K99DA030908, R00DA030908, 5P01DA009789, P01DA01725, AG028040, R03DA027936, DA026261, T32DA007027]
- Institute for Drug and Alcohol Studies at Virginia Commonwealth University
- Ellison Medical Foundation
- Skaggs Institute for Chemical Biology
Ask authors/readers for more resources
Phospholipase A(2)(PLA(2)) 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 PLA(2). 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available