Monoacylglycerol lipase contributes to pathogenesis of Alzheimer's 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...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Published: |
Elsevier
2017
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| Online Access: | http://hdl.handle.net/1721.1/112276 https://orcid.org/0000-0002-8021-277X |
| Summary: | 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. |
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