Abstract
Social stress has a high impact on many biological systems in the brain, including serotonergic (5-HT) system—a major drug target in the current treatment for depression. Hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis and monoamine oxidase A (MAO-A) are well-known stress responses, which are involved in the central 5-HT system. Although, many MAO-A inhibitors have been developed and used in the therapeutics of depression, effective management of depression by modulating the activity of MAO-A has not been achieved. Identifying the molecular pathways that regulate the activity of MAO-A in the brain is crucial for developing new drug targets for precise control of MAO-A activity. Over the last few decades, several regulatory pathways of MAO-A consisting of Kruppel like factor 11 (KLF11), Sirtuin1, Ring finger protein in neural stem cells (RINES), and Cell division cycle associated 7-like protein (R1) have been identified, and the influence of social stress on these regulatory factors evaluated. This review explores various aspects of these pathways to expand our understanding of the roles of the HPA axis and MAO-A regulatory pathways during social stress. The first part of this review introduces some components of the HPA axis, explains how stress affects them and how they interact with the 5-HT system in the brain. The second part summarizes the novel regulatory pathways of MAO-A, which have high potential as novel therapeutic targets for depression.
Highlights
Depression is one of the most prevalent mental disorders (Kessler and Bromet, 2013)
There is evidence that social stress can lead to depression, which is mediated by the HPA-axis and the central 5-HT system
MAOA inhibitors are selectively used in therapeutics for depression due to their adverse effects (Shulman et al, 2009; Menkes et al, 2016) caused by the inhibition of monoamine oxidase A (MAO-A) in non-specific brain regions
Summary
Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia. Social stress has a high impact on many biological systems in the brain, including serotonergic (5-HT) system—a major drug target in the current treatment for depression. Identifying the molecular pathways that regulate the activity of MAO-A in the brain is crucial for developing new drug targets for precise control of MAO-A activity. This review explores various aspects of these pathways to expand our understanding of the roles of the HPA axis and MAO-A regulatory pathways during social stress. The first part of this review introduces some components of the HPA axis, explains how stress affects them and how they interact with the 5-HT system in the brain. The second part summarizes the novel regulatory pathways of MAO-A, which have high potential as novel therapeutic targets for depression
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