Monoamine oxidase A (MAOA) is a mitochondrial enzyme that catalyzes the oxidative deamination of monoamine neurotransmitters and dietary amines. It is involved in the degradation of norepinephrine, epinephrine, and serotonin, and has a significant impact on neurological function [1,2].

MAOA has been linked to various diseases. In prostate cancer, it plays a key role in almost each stage, including castrate-resistant prostate cancer, neuroendocrine prostate cancer, metastasis, drug resistance, stemness, and perineural invasion. MAOA inhibitor treatment effectively reduces perineural invasion of prostate cancer cells in vitro and suppresses xenograft tumor growth in mice [1,4]. In gastric cancer, MAOA expression is downregulated, and its overexpression can suppress tumor growth and glycolysis, and promote cancer cell apoptosis through the PI3K/Akt/mTOR pathway [2]. MAOA deficiency in some males from a Dutch kindred was associated with borderline mental retardation and increased impulsive behavior, although it doesn't constitute an “aggression gene” [3]. Also, methylation of the MAOA promoter is associated with schizophrenia [5].

In conclusion, MAOA is crucial for the regulation of neurotransmitter levels. Research on MAOA, especially through the use of models like inhibitor treatments (function-inhibiting approaches similar to loss-of-function in concept), has revealed its significance in diseases such as prostate cancer, gastric cancer, and mental disorders. Understanding MAOA's functions provides potential therapeutic targets for these diseases.

References:

1. Han, Hao, Li, Hui, Ma, Yifan, Zhao, Jumei, Shi, Changhong. 2023. Monoamine oxidase A (MAOA): A promising target for prostate cancer therapy. In Cancer letters, 563, 216188. doi:10.1016/j.canlet.2023.216188. https://pubmed.ncbi.nlm.nih.gov/37076041/

2. Wang, Yang-Yang, Zhou, Yao-Qi, Xie, Jia-Xuan, Zhao, En-Hao, Li, Jun. 2023. MAOA suppresses the growth of gastric cancer by interacting with NDRG1 and regulating the Warburg effect through the PI3K/AKT/mTOR pathway. In Cellular oncology (Dordrecht, Netherlands), 46, 1429-1444. doi:10.1007/s13402-023-00821-w. https://pubmed.ncbi.nlm.nih.gov/37249744/

3. Brunner, H G. . MAOA deficiency and abnormal behaviour: perspectives on an association. In Ciba Foundation symposium, 194, 155-64; discussion 164-7. doi:. https://pubmed.ncbi.nlm.nih.gov/8862875/

4. Yin, Lijuan, Li, Jingjing, Wang, Jing, Li, Qinlong, Wu, Boyang Jason. 2021. MAOA promotes prostate cancer cell perineural invasion through SEMA3C/PlexinA2/NRP1-cMET signaling. In Oncogene, 40, 1362-1374. doi:10.1038/s41388-020-01615-2. https://pubmed.ncbi.nlm.nih.gov/33420365/

5. Yang, Hao, Li, Jiajue, Ji, Aicen, Yan, Ming, Nie, Shengjie. . Methylation of the MAOA promoter is associated with schizophrenia. In Annals of translational medicine, 8, 864. doi:10.21037/atm-20-4481. https://pubmed.ncbi.nlm.nih.gov/32793708/