Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease

Rongqing Chen, Jian Zhang, Yan Wu, Dongqing Wang, Guoping Feng, Ya Ping Tang, Zhaoqian Teng, Chu Chen

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1329-1339
Number of pages11
JournalCell Reports
Volume2
Issue number5
DOIs
StatePublished - Nov 29 2012
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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