Targeting Monoamine Oxidases: From Enzymatic Function to Pharmaceutical Use
A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".
Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 8415
Special Issue Editor
Interests: monoamines; neurochemistry; addiction; Parkinson's disease; schizophrenia; neuropharmacology; mood disorders
Special Issues, Collections and Topics in MDPI journals
Special Issue Information
Dear Colleagues,
Monoamine oxidases A and B (MAOA and MAOB) play an essential role in the oxidation of monoamines, and participate in the oxidative metabolism of both the central nervous system (CNS) and peripheral tissue. They are attached to the external membrane of mitochondria and oxidize the substrate amino group through the enzyme-bound FAD cofactor, which is then reoxidized by molecular oxygen with the release of hydrogen peroxide. MAOA and MAOB are involved in the regulation of concentrations of biogenic amines dopamine, noradrenaline, adrenaline, and serotonin in monoaminergic neurons and likely in other cell types. Their metabolism is still complex, as the distribution of MAOA and MAOB does not necessarily match the preferred biogenic amine substrate, and MAOA and MAOB are also involved in the degradation of some their metabolites.
MAOA and/or MAOB are a possible target in a number of diseases related to oxidative stress and biogenic amine defects. MAOB inhibitors are given in the treatment of Parkinson’s disease, whereas mixed MAOA/B or MAOA inhibitors have antidepressant properties. Their antioxidant properties repurpose their use in neurodegenerative diseases, notably Alzheimer’s disease, stroke, cardiovascular diseases, and obesity, to cite a few. Naturally ingested compounds, such as harmane, curcumin, and b-carbolines are potential antioxidant compounds that have an inhibitory effect on MAOs. Some of them, not always fully identified, are thought to participate in the psychoactive action of tobacco or ayahuasca by reducing MAO activity. These natural compounds serve to develop several series of potent MAO inhibitors, while the availability of MAO crystal structures has led to the optimization of drug design in in silico studies. Chemical research in the field of MAO is very active to produce either new potent and selective compounds or multitarget drugs that show inhibitory activity on MAOs.
The path is quite clear, but there are still many questions on their function that start from the reaction of the catalyse itself, which can be apprehended either experimentally or through computational studies. Their impact on the metabolism of amines and biogenic amines is still opaque. The MAO blockade has consequences on endogenous monoamines, trace amine concentrations, and exogenous amines from alimentation. The regulation of their expression, the modification of their activity through drugs or environmental conditions, and the existence of polymorphisms could produce monoamine imbalance. Thus, a further step in understanding the implication of MAOs in diseases regards the availability of PET radioligand tools aiming at revealing the distribution and quantity of MAOA/B in various conditions in preclinical and clinical studies.
The purpose of this Special Issue is to collect research articles and reviews at different levels of analysis dealing with the functions of MAOA and MAOB, and the development of inhibitors. Chemical, molecular, biochemical, and biological studies are welcome in this Special Issue.
Prof. Philippe De Deurwaerdère
Guest Editor
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Keywords
- Monoamine oxidase inhibitor
- biochemistry
- amine metabolism
- behaviour
- peripheral organs
- central nervous system
- neurochemistry
- oxidative stress
- neurodegenerative disease
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