A comprehensive review of monoamine oxidase inhibitors as Anti-Alzheimer's disease agents: A review

Eur J Med Chem. 2020 Nov 15:206:112787. doi: 10.1016/j.ejmech.2020.112787. Epub 2020 Sep 1.

Abstract

Monoamine oxidases (MAO-A and MAO-B) are mammalian flavoenzyme, which catalyze the oxidative deamination of several neurotransmitters like norepinephrine, dopamine, tyramine, serotonin, and some other amines. The oxidative deamination produces several harmful side products like ammonia, peroxides, and aldehydes during the biochemical reaction. The concentration of biochemical neurotransmitter alteration in the brain by MAO is directly related with several neurological disorders like Alzheimer's disease and Parkinson's disease (PD). Activated MAO also contributes to the amyloid beta (Aβ) aggregation by two successive cleft β-secretase and γ-secretase of amyloid precursor protein (APP). Additionally, activated MAO is also involved in aggregation of neurofibrillary tangles and cognitive destruction through the cholinergic neuronal damage and disorder of the cholinergic system. MAO inhibition has general anti-Alzheimer's disease effect as a consequence of oxidative stress reduction prompted by MAO enzymes. In this review, we outlined and addressed recent understanding on MAO enzymes such as their structure, physiological function, catalytic mechanism, and possible therapeutic goals in AD. In addition, it also highlights the current development and discovery of potential MAO inhibitors (MAOIs) from various chemical scaffolds.

Keywords: Alzheimer’s disease; Monoamine oxidase enzyme; Monoamine oxidase inhibitors; Neurotransmitter amines.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / enzymology
  • Alzheimer Disease / pathology
  • Animals
  • Drug Discovery*
  • Humans
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology

Substances

  • Monoamine Oxidase Inhibitors
  • Monoamine Oxidase