Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease
Name
Chen-2012-Monoacylglycerol Lip.pdf
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Author(s)
Chen, Rongqing
Zhang, Jian
Wu, Yan
Wang, Dongqing
Feng, Guoping
Tang, Ya-Ping
Teng, Zhaoqian
Chen, Chu
Date Issued
November 2012
Journal
Cell Reports
Publisher
Elsevier B.V.
Citation
Chen, Rongqing, Jian Zhang, Yan Wu, Dongqing Wang, Guoping Feng, Ya-Ping Tang, Zhaoqian Teng, and Chu Chen. “Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer’s Disease.” Cell Reports 2, no. 5 (November 2012): 1329–1339.
Version
Final published version
Abstract
Alzheimer's disease (AD) is the most common cause of dementia among older people. There are no effective medications currently available to prevent and treat AD and halt disease progression. Monoacylglycerol lipase (MAGL) is the primary enzyme metabolizing the endocannabinoid 2-arachidonoylglycerol in the brain. We show here that inactivation of MAGL robustly suppressed production and accumulation of β-amyloid (Aβ) associated with reduced expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) in a mouse model of AD. MAGL inhibition also prevented neuroinflammation, decreased neurodegeneration, maintained integrity of hippocampal synaptic structure and function, and improved long-term synaptic plasticity, spatial learning, and memory in AD animals. Although the molecular mechanisms underlying the beneficial effects produced by MAGL inhibition remain to be determined, our results suggest that MAGL, which regulates endocannabinoid and prostaglandin signaling, contributes to pathogenesis and neuropathology of AD, and thus is a promising therapeutic target for the prevention and treatment of AD.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2012.09.030
