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Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons

  • Neurology and Preclinical Neurological Studies - Review Article
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Abstract

Type A and B monoamine oxidases (MAO-A, -B) mediate and modulate intracellular signal pathways for survival or death of neuronal cells. MAO-A is associated with development of neuronal architecture, synaptic activity, and onset of psychiatric disorders, including depression, and antisocial aggressive impulsive behaviors. MAO-B produces hydrogen peroxide and plays a vital role in neuronal loss of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. This review presents a novel role of MAO-A and B, their substrates and inhibitors, and hydrogen peroxide in brain function and neuronal survival and death. MAO-A activity is regulated not only by genetic factor, but also by environmental factors, including stress, hormonal deregulation, and food factors. MAO-A activity fluctuates by genetic–environmental factors, modulates the neuronal response to the stimuli, and affects behavior and emotional activities. MAO-B inhibitors selegiline and rasagiline protect neurons via increase expression of anti-apoptotic Bcl-2 and pro-survival neurotrophic factors in human neuroblastoma SH-SY5Y and glioblastoma U118MG cell lines. MAO-A knockdown suppressed the rasagiline-induced gene expression in SH-SY5Y cells, whereas MAO-B silencing enhanced the basal- and selegiline-induced gene expression in U118MG cells. MAO-A and B were shown to function as a mediator or repressor of gene expression, respectively. Further study on cellular mechanism underlying regulation of signal pathways by MAO-A and B may bring us a new insight on the role of MAOs in decision of neuronal fate and the development of novel therapeutic strategy may be expected for neuropsychiatric disorders.

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Abbreviations

ERK:

Extracellular signal-regulated protein kinase

ETC:

Electron transfer chain

KLF:

Krüppel-like factor

MAO-A and MAO-B:

Type A and B monoamine oxidase

mao-A and mao-B KD, KO:

MAO-A and MAO-B knockdown, knockout

NHLH2:

Nescient helix-loop-helix 2

NTF:

Neurotrophic factor

PI3K:

Phosphatidylinisitol-3 kinase

siMao-A, siMao-B, siNS :

siRNA against mao-A and mao-B, and non-specific

Sp1:

Specificity protein 1

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  1. Department of Health and Nutrition, Faculty of Psychological and Physical Science, Aichi Gakuin University, 12 Araike, Iwasaki-cho, Nisshin, 320-0195, Aichi, Japan

    Makoto Naoi, Wakako Maruyama & Masayo Shamoto-Nagai

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Naoi, M., Maruyama, W. & Shamoto-Nagai, M. Type A and B monoamine oxidases distinctly modulate signal transduction pathway and gene expression to regulate brain function and survival of neurons. J Neural Transm 125, 1635–1650 (2018). https://doi.org/10.1007/s00702-017-1832-6

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