Mar 24, 2020

Potential application of endocannabinoid system agents in neuropsychiatric and neurodegenerative diseases-focusing on FAAH/MAGL inhibitors

Acta Pharmacologica Sinica
Si-Yu RenNai-Hong Chen

Abstract

The endocannabinoid system (ECS) has received extensive attention for its neuroprotective effect on the brain. This system comprises endocannabinoids, endocannabinoid receptors, and the corresponding ligands and proteins. The molecular players involved in their regulation and metabolism are potential therapeutic targets for neuropsychiatric diseases including anxiety, depression and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The inhibitors of two endocannabinoid hydrolases, i.e., fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), have the capacity to increase the level of endocannabinoids indirectly, causing fewer side effects than those associated with direct supplementation of cannabinoids. Their antidepressant and anxiolytic mechanisms are considered to modulate the hypothalamic-pituitary-adrenal axis and regulate synaptic and neural plasticity. In terms of AD/PD, treatment with FAAH/MAGL inhibitors leads to reduction in amyloid β-protein deposition and inhibition of the death of dopamine neurons, which are commonly accepted to underlie the pathogenesis of AD and PD, respectively. Inflammation as the cause of depression/anxiety and PD/AD is also the target of ...Continue Reading

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Mentioned in this Paper

Pathogenesis
Alzheimer's Disease
Cessation of Life
Metabolism
Inhibitors
Progressive Disease
Endocannabinoids
Synapses
Fatty acid amide hydrolase
Dopamine

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