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

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

Publication date: Mar 18, 2020

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 ?-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 FAAH/MAGL inhibitors. In this review, we summarize the application and involvement of FAAH/MAGL inhibitors in related neurological diseases. Focus on the latest research progress using FAAH/MAGL inhibitors is expected to facilitate the development of novel approaches with therapeutic potential.

Ren, S.Y., Wang, Z.Z., Zhang, Y., and Chen, N.H. Potential application of endocannabinoid system agents in neuropsychiatric and neurodegenerative diseases-focusing on FAAH/MAGL inhibitors. 24443. 2020 Acta Pharmacol Sin.

Concepts Keywords
Adrenal Anxiety depression
Alzheimer Inflammation
Amyloid Neuropsychiatric neurodegenerative diseases
Antidepressant Cannabinoids
Anxiety Branches of biology
Anxiolytic Neurochemistry
Brain Monoacylglycerol lipase
Cannabinoids Endocannabinoid system
Depression Carbamates
Dopamine Biochemistry
Endocannabinoid Endocannabinoid enhancer
Endocannabinoid System JZL195
Endocannabinoids
FAAH
Hypothalamic
Inflammation
Ligands
Metabolism
Neural Plasticity
Neurodegenerative Diseases
Neurological Diseases
Neurons
Neuroprotective
Neuropsychiatric
Parkinson
Pathogenesis
Pituitary
Protein
Receptors
Synaptic

Semantics

Type Source Name
disease MESH neurodegenerative diseases
pathway REACTOME Neurodegenerative Diseases
disease MESH anxiety
disease MESH depression
disease MESH death
drug DRUGBANK Dopamine
disease MESH Inflammation
disease MESH development

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