Premium
P4‐190: Monoacylglycerol lipase contributes to pathogenesis of Alzheimer's disease
Author(s) -
Chen Rongqing,
Zhang Jian,
Wu Yan,
Wang Dongqing,
Feng Guoping,
Tang YaPing,
Chen Chu
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.1894
Subject(s) - monoacylglycerol lipase , long term potentiation , endocannabinoid system , synaptic plasticity , neuroprotection , amyloid precursor protein , neuroscience , neuroinflammation , dendritic spine , diacylglycerol lipase , amyloid beta , neurotransmission , biology , chemistry , hippocampal formation , pharmacology , alzheimer's disease , medicine , biochemistry , inflammation , receptor , immunology , peptide , disease
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. While the molecular mechanisms underlying MAGL inhibition-produced beneficial effects 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.National Institutes of Health (U.S.) (Grant R01NS076815)National Institutes of Health (U.S.) (Grant R01NS054886