Special issue on monoamine oxidase, titled “Monoamine Oxidase Isoenzymes: Eternally Enigmatic Enzyme”

Foreword:

For the special issue on monoamine oxidase, titled “Monoamine Oxidase Isoenzymes: Eternally Enigmatic Enzyme”

After Mary L. C. Hare (later, Bernheim) reported the enzyme catalyzing oxidation of monoamines, later called as monoamine oxidase (MAO) in 1928, the structure, function and regulation of expression have been intensively studied. MAO was clearly identified as two independent protein species coded by different genes with selective affinity to substrates and inhibitors in 1988. These MAOs exhibit identical intron and exon organization derived from duplication of a common ancestral gene more than a million years ago, thus they are MAO A and B isoenzymes. MAO A and MAO B are localized to distinct cell types and tissues, with specific functions in the brain and peripheral tissues. MAO is associated with the regulation of monoamine neurotransmitters and is important for the development and maintenance of neuronal architecture and circuits. Further, MAO regulates motor coordination, cognition, multiple behaviors, mood and emotion, and recently has been implicated in carcinogenesis. MAO A and B knockout mouse studies demonstrate through “gene- environment interactions” that MAO A is involved in emotional behaviors such as aggression, anxiety, impulsivity, and anti-social behaviors. MAO A and B inhibitors were developed as L-DOPA adjuncts and anti-depressants. Mechanistic investigations have yielded novel therapeutic strategies including neuroprotection in aging, neurodegenerative and depressive disorders. MAO has been shown to play a decisive role in cellular death and survival by its involvement in cellular signaling pathways and the mitochondrial apoptosis cascade.

Research on MAO has been developed through continuous discussion and cooperation among scientific investigators from different countries and research fields. The “Amine Oxidase Meeting” organized every two years in both global hemispheres has given us valuable opportunities to advance MAO research and form close lifelong friendships. As one generation of MAO researchers, we summarize our discoveries on MAO with challenging unanswered questions for the next generation to discover. In this special issue on MAO, we collectively merge historical discoveries with our latest findings on the enzymatic, pharmacological, genetic and environmental factors that influence MAO function with impact on a spectrum of neuropsychiatric disorders and cancers. In addition, the present and future aspects of MAO inhibitors are reviewed. We hope that this special issue on MAO will be able to help the readers to find new concepts for future study on MAO, based on what we have found.