Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease

被引：242

作者：

Chen, Rongqing ^{[1
]}

Zhang, Jian ^{[1
]}

Wu, Yan ^{[1
]}

Wang, Dongqing ^{[3
,4
]}

Feng, Guoping ^{[3
,4
]}

Tang, Ya-Ping ^{[2
]}

Teng, Zhaoqian ^{[1
]}

Chen, Chu ^{[1
]}

机构：

[1] Louisiana State Univ, Hlth New Orleans Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA 70112 USA

[2] Louisiana State Univ, Hlth New Orleans Sci Ctr, Sch Med, Dept Anat & Cell Biol, New Orleans, LA 70112 USA

[3] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA

[4] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

来源：

CELL REPORTS | 2012年 / 2卷 / 05期

关键词：

ENDOCANNABINOID; 2-ARACHIDONOYLGLYCEROL; TRANSGENIC MICE; CANNABINOID RECEPTORS; SYNAPTIC PLASTICITY; MEMORY; EXPRESSION; NEURONS; NEUROINFLAMMATION; ACCUMULATION; TRANSMISSION;

D O I：

10.1016/j.celrep.2012.09.030

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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 beta-amyloid (A beta) associated with reduced expression of beta-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.

引用

页码：1329 / 1339

页数：11

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