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Cell Rep DOI:10.1016/j.celrep.2012.09.030

Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease.

Publication TypeJournal Article
Year of Publication2012
AuthorsChen, R, Zhang, J, Wu, Y, Wang, D, Feng, G, Tang, Y-P, Teng, Z, Chen, C
JournalCell Rep
Date Published2012 Nov 29
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Amyloid Precursor Protein Secretases, Animals, Aspartic Acid Endopeptidases, Astrocytes, Benzodioxoles, Disease Models, Animal, Down-Regulation, Hippocampus, Humans, Mice, Mice, Transgenic, Microglia, Monoacylglycerol Lipases, Neuronal Plasticity, Piperidines, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Synapses

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.


Alternate JournalCell Rep
PubMed ID23122958
PubMed Central IDPMC3513645
Grant ListR01 NS076815 / NS / NINDS NIH HHS / United States
R01 NS054886 / NS / NINDS NIH HHS / United States
R21 AG039669 / AG / NIA NIH HHS / United States
R01NS054886 / NS / NINDS NIH HHS / United States
R01NS076815 / NS / NINDS NIH HHS / United States
R21AG039669 / AG / NIA NIH HHS / United States