What is the phenotype of the mutated monoamine oxidase?

A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity.

What is the method for measuring MAO B?

Although platelets are a convenient source for measurement of MAO B as a biomarker,the best method to examine the levels of MAO A and MAO B in the brain is by Positron Emission Tomography (PET).

What is the phenotype of MAO B in the neonate?

MAO B is low in the neonate both in mice and humans, but increases rapidly after birth (Holschneider et al., 2001, Nicotra et al., 2004).

What is the recent meta-analysis of 20 studies?

A recent meta-analysis of twenty studies with 2846 patients and 3508 controls provides evidence for a slightly increased risk of PD with the G allele (Liu et al., 2014).

How long did the recovery of MAO B take?

The recovery of MAO B in human brain was followed using PET, revealing a recovery period of about 40 days (Fowler et al., 2005, Fowler et al., 2015).spectrum, mass, and crystal structure of the adduct.

What is the ligand for the imidazoline2 binding site?

Evaluation and initial in vitro and ex vivo characterization of the potential positron emission tomography ligand, BU99008 (2-(4,5-Dihydro-1H-imidazol-2-yl)-1-methyl-1H-indole), for the imidazoline2 binding site.

What is the kinetics of binding to MAO B?

High affinity (nM) binding to MAO B was first demonstrated using various I2 ligands in a small proportion of native human MAO B heterologously expressed in yeast (Tesson et al., 1995), and further explored in detailed kinetic and binding experiments (McDonald et al., 2010).

What is the mechanism of metabolizing dopamine and noradrenaline?

From these kinetic measurements, it is clear that dopamine and noradrenaline are metabolized by both MAO A and MAO B, but serotonin is metabolized mainly by MAO A.

Open AccessJournal Article10.1016/J.PNPBP.2016.02.005

Molecular aspects of monoamine oxidase B.

Rona R. Ramsay

- 01 Aug 2016

- Progress in Neuro-psychopharmacology & B...

- Vol. 69, pp 81-89

TL;DR: Examples of recent research on the molecular aspects of the expression, activity, and inhibition of MAO B are focused on, including the effect of DNA methylation on the expression.

Abstract: Monoamine oxidases (MAO) influence the monoamine levels in brain by virtue of their role in neurotransmitter breakdown. MAO B is the predominant form in glial cells and in platelets. MAO B structure, function and kinetics are described as a background for the effect of alterations in its activity on behavior. The need to inhibit MAO B to combat decreased brain amines continues to drive the search for new drugs. Reversible and irreversible inhibitors are now designed using data-mining, computational screening, docking and molecular dynamics. Multi-target ligands designed to combat the elevated activity of MAO B in Alzheimer's and Parkinson's Diseases incorporate MAO inhibition (usually irreversible) as well as iron chelation, antioxidant or neuroprotective properties. The main focus of drug design is the catalytic activity of MAO, but the imidazoline I2 site in the entrance cavity of MAO B is also a pharmacological target. Endogenous regulation of MAO B expression is discussed briefly in light of new studies measuring mRNA, protein, or activity in healthy and degenerative samples, including the effect of DNA methylation on the expression. Overall, this review focuses on examples of recent research on the molecular aspects of the expression, activity, and inhibition of MAO B.

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Most frequently asked questions

1. What is the way to measure MAO B?

An irreversible ligand such as deprenyl requires active MAO B to form the adduct, so servesas an in vivo measurement of both protein and activity; reversible ligands measure only protein levels.

2. What is the role of amine transporters in the oxidative stress of the heart?

Activated platelets release serotonin during cardiac ischemia, some of which is taken up by amine transporters into the cardiomyocytes.

3. What is the way to inhibit MAO B in vivo?

Only labazemide, with a nanomolar Ki as a result of the slow dissociation of its complex with MAO B, along with moclobemide for MAO A have been used in the clinic.

4. What is the role of the MAO B in serotonergic neurons?

Since serotonergic neurons contain mainly MAO B, this is consistent with a role for the MAO B in serotonergic neurons to protect mitochondria and the nerve terminals from other neurotransmitters.

Fig. 1. Promotor and transcriptional regulation of MAO B (adapted from (Shih et al., 2011).

Fig. 2. MAO B monomer structure. The two views of MAO B were prepared from pdb file 1oja using AutoDock. The bound isatin was removed, the covalent bond between the FAD and Cys 198 inserted, and hydrogen atoms added. The FAD and the tyrosines that form the aromatic cage around the active site are shown as sticks; the general structure is shown in ribbon form. A. Side view showing the helix that is buried in the membrane; the active site cavity bounded by FAD and three tyrosines is seen in the middle. B. View looking up from the membrane through the entrance cavity to the active site.

Fig. 3. Kinetic cycle of MAO B. The scheme shows two forms of MAO B (E, oxidized and F, reduced) both of which can bind substrate (S) or product (P) reversibly. The reduction step (kr) is the slowest step. There are three possible forms of the reduced enzyme (FP, F, and FS in red square boxes) each of which reacts with oxygen at a different rate (ko, ko’, ko’’) to return to the equivalent oxidized form of the enzyme (in blue circles)

Citations

Journal Article•10.1021/ACS.CHEMREV.8B00538

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.

Giray Enkavi, +5 more

- 12 Mar 2019

- Chemical Reviews

TL;DR: This review discusses the current state-of-the-art of biomembrane simulations that, until now, have largely focused on a rather narrow picture of the complexity of the membranes, and discusses the challenges that should unravel in the foreseeable future.

...read moreread less

274

Journal Article•10.1002/MED.21561

Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update

Rati K. P. Tripathi, +2 more

- 01 Sep 2019

- Medicinal Research Reviews

TL;DR: This review summarizes the current understanding on MAO‐A/MAO‐B including their structure, catalytic mechanism, and biological functions with emphases on the role of MAo‐B as a potential therapeutic target for the development of medications treating neurodegenerative disorders.

...read moreread less

Journal Article•10.1021/ACS.JPCB.6B09011

Empirical Valence Bond Simulations of the Hydride-Transfer Step in the Monoamine Oxidase A Catalyzed Metabolism of Noradrenaline

Matej Repič, +6 more

- 26 Oct 2016

- Journal of Physical Chemistry B

TL;DR: At atomistic empirical valence bond simulations of the rate-limiting step of the MAO-A-catalyzed NA (norepinephrine) degradation, involving hydride transfer from the substrate α-methylene group to the flavin moiety of the Flavin adenine dinucleotide prosthetic group, strongly support the fact that both MAo-A andMAO-B isoforms function by the samehydride-transfer mechanism.

...read moreread less

Journal Article•10.4155/FMC-2017-0036

Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's disease.

Damijan Knez, +3 more

- 15 May 2017

- Future Medicinal Chemistry

TL;DR: The aim of this review is to provide an update on the novel dual inhibitors identified recently and to shed light on their therapeutic potential.

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Journal Article•10.1016/J.EJMECH.2018.02.015

Novel indanone derivatives as MAO B/H3R dual-targeting ligands for treatment of Parkinson's disease.

Anna Affini, +4 more

- 25 Mar 2018

- European Journal of Medicinal Chemistry

TL;DR: Indanone-substituted derivatives are promising lead structures for the design of MAO B/hH3R DTLs as novel therapeutic approach of PD therapy.

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References

Journal Article•10.1038/NRN1537

Iron, brain ageing and neurodegenerative disorders

Luigi Zecca, +4 more

- 01 Nov 2004

- Nature Reviews Neuroscience

TL;DR: By studying the accumulation and cellular distribution of iron during ageing, this work should be able to increase the understanding of these neurodegenerative disorders and develop new therapeutic strategies.

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Journal Article•10.1126/SCIENCE.8211186

Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

Han G. Brunner, +4 more

- 22 Oct 1993

- Science

TL;DR: Analytical results indicate that isolated complete MAOA deficiency in this family is associated with a recognizable behavioral phenotype that includes disturbed regulation of impulsive aggression.

...read moreread less

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Journal Article•10.1038/NRN1883

The therapeutic potential of monoamine oxidase inhibitors.

Moussa B.H. Youdim, +2 more

- 01 Apr 2006

- Nature Reviews Neuroscience

TL;DR: This work evaluates claims and some counter-claims made about the physiological importance of these enzymes and the potential of their inhibitors in the light of what the authors know, and still have to learn, of the structure, function and genetics of the monoamine oxidases and the disparate actions of their inhibitor.

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•Journal Article•10.1146/ANNUREV.NEURO.22.1.197

Monoamine oxidase: from genes to behavior.

Jean C. Shih, +2 more

- 01 Jan 1999

- Annual Review of Neuroscience

TL;DR: MAO A and B knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders and show increased reactivity to stress.

...read moreread less

1.2K

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Molecular aspects of monoamine oxidase B.

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AI Agents for this Paper

Most frequently asked questions

1. What is the way to measure MAO B?

2. What is the role of amine transporters in the oxidative stress of the heart?

3. What is the way to inhibit MAO B in vivo?

4. What is the role of the MAO B in serotonergic neurons?

5. What is the phenotype of the mutated monoamine oxidase?

6. What is the method for measuring MAO B?

7. What is the phenotype of MAO B in the neonate?

8. What is the recent meta-analysis of 20 studies?

9. How long did the recovery of MAO B take?

10. What is the ligand for the imidazoline2 binding site?

11. What is the kinetics of binding to MAO B?

12. What is the mechanism of metabolizing dopamine and noradrenaline?

Figures

Citations

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance.

Monoamine oxidase-B inhibitors as potential neurotherapeutic agents: An overview and update

Empirical Valence Bond Simulations of the Hydride-Transfer Step in the Monoamine Oxidase A Catalyzed Metabolism of Noradrenaline

Dual inhibitors of cholinesterases and monoamine oxidases for Alzheimer's disease.

Novel indanone derivatives as MAO B/H3R dual-targeting ligands for treatment of Parkinson's disease.

References

Iron, brain ageing and neurodegenerative disorders

Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A

The therapeutic potential of monoamine oxidase inhibitors.

Monoamine oxidase: from genes to behavior.

Inhibition of monoamine oxidase B in the brains of smokers

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