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

Cell reports | Nov 29, 2012

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.

Pubmed ID: 23122958 RIS Download

Mesh terms: Alzheimer Disease | Amyloid Precursor Protein Secretases | Amyloid beta-Peptides | Amyloid beta-Protein Precursor | 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

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Associated grants

  • Agency: NINDS NIH HHS, Id: R01 NS076815
  • Agency: NINDS NIH HHS, Id: R01 NS054886
  • Agency: NIA NIH HHS, Id: R21 AG039669
  • Agency: NINDS NIH HHS, Id: R01NS054886
  • Agency: NINDS NIH HHS, Id: R01NS076815
  • Agency: NIA NIH HHS, Id: R21AG039669

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A software application which allows reconstruction of neuronal structures from confocal and multi-photon images. NeuronStudio provides tools for manual, semi-manual, and automatic tracing of the dendritic arbor, as well as manual and automatic detection and classification of dendritic spines. Advanced 2D and 3D visualization techniques facilitate the verification of the reconstruction, as well as allowing accurate manual editing. The most current version is Version 0.9.92 which was last updated on November 19, 2009.

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