Monoacylglycerol Lipase Is a Therapeutic Target for 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-arachidonoylglyc...
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2014
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| Online Access: | http://hdl.handle.net/1721.1/91650 https://orcid.org/0000-0002-8021-277X |
| _version_ | 1826200406897721344 |
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| author | Chen, Rongqing Zhang, Jian Wu, Yan Wang, Dongqing Feng, Guoping Tang, Ya-Ping Teng, Zhaoqian Chen, Chu |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Chen, Rongqing Zhang, Jian Wu, Yan Wang, Dongqing Feng, Guoping Tang, Ya-Ping Teng, Zhaoqian Chen, Chu |
| author_sort | Chen, Rongqing |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:35:55Z |
| format | Article |
| id | mit-1721.1/91650 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:35:55Z |
| publishDate | 2014 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/916502022-09-27T20:35:50Z Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease Chen, Rongqing Zhang, Jian Wu, Yan Wang, Dongqing Feng, Guoping Tang, Ya-Ping Teng, Zhaoqian Chen, Chu Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Wang, Dongqing Feng, Guoping 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. National Institutes of Health (U.S.) (NIH grant R01NS076815) National Institutes of Health (U.S.) (NIH Grant R01NS054886) National Institutes of Health (U.S.) (NIH Grant R21AG039669) 2014-11-20T16:38:22Z 2014-11-20T16:38:22Z 2012-11 2012-06 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/91650 Chen, Rongqing, Jian Zhang, Yan Wu, Dongqing Wang, Guoping Feng, Ya-Ping Tang, Zhaoqian Teng, and Chu Chen. “Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer’s Disease.” Cell Reports 2, no. 5 (November 2012): 1329–1339. https://orcid.org/0000-0002-8021-277X en_US http://dx.doi.org/10.1016/j.celrep.2012.09.030 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Chen, Rongqing Zhang, Jian Wu, Yan Wang, Dongqing Feng, Guoping Tang, Ya-Ping Teng, Zhaoqian Chen, Chu Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease |
| title | Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease |
| title_full | Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease |
| title_fullStr | Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease |
| title_full_unstemmed | Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease |
| title_short | Monoacylglycerol Lipase Is a Therapeutic Target for Alzheimer's Disease |
| title_sort | monoacylglycerol lipase is a therapeutic target for alzheimer s disease |
| url | http://hdl.handle.net/1721.1/91650 https://orcid.org/0000-0002-8021-277X |
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