Abstract
Monoamine oxidase A (MAO-A) is an enzyme that regulates the levels of monoamine neurotransmitters, such as serotonin, noradrenaline and dopamine and it has been used as a therapeutic target for depression. However, MAO-A inhibitors, which directly acts on MAO-A protein, have limited use due to their adverse effects. microRNAs (miRNAs) are 18–22 nucleotide long, small non-coding RNAs, which have recently emerged as regulators of protein levels that could potentially be new therapeutic targets for psychiatric disorders. This review article aims to discuss the current status of the treatment for depression with MAO-A inhibitors and the regulatory factors of MAO-A. Further, the review also proposes possible regulatory mechanisms of MAO-A by miRNAs, which leads to better understanding of the pathology of depressive disorders and their potential use as therapeutic agents.
Highlights
Depression is the most prevalent mental disorder worldwide (Ferrari et al, 2013; Kessler and Bromet, 2013)
We address a question; Can microRNAs be prominent therapeutic targets for depression by regulating monoamine oxidase A (MAO-A) in the brain?
Several studies suggest that miRNAs indirectly regulate MAO-A by targeting the regulators of MAO-A expression, such as SIRT1, indicating the potential of miRNAs as therapeutic targets
Summary
Depression is the most prevalent mental disorder worldwide (Ferrari et al, 2013; Kessler and Bromet, 2013). Microarray study showed higher expression levels of miR-22 in the brain tissues of rat, such as the hippocampus, olfactory bulb, brain stem, cortex and hypothalamus, compared to the peripheral organs, including the heart, liver, kidney and lung (Hua et al, 2009), suggesting that miR-22 is brain-enriched miRNA. Elucidating the relationship between miRNAs and these regulatory factors would be useful to find miRNAs which can be novel therapeutic targets for better control of MAO-A in the brain Another possible mechanism by which miRNAs changes MAO-A levels is that miRNAs directly target MAO-A mRNA as proposed about miR-132 (Xiao J. et al, 2014; Figure 1) and miR-22 (Muiños-Gimeno et al, 2011; Figure 1). The techniques to modulate the function of miRNAs in the brain are important issues which may decide whether miRNAs can be potential therapeutic targets for depression
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