Monoamine oxidase as a target for the development of new drugs
- Authors: Romanycheva A.A.1, Fedorov V.N.1, Shetnev A.A.1, Korsakov M.K.1
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Affiliations:
- Yaroslavl State Pedagogical University named after K.D. Ushinsky
- Issue: Vol 28, No 2 (2025)
- Pages: 3-11
- Section: Pharmaceutical chemistry
- URL: https://journals.eco-vector.com/1560-9596/article/view/658375
- DOI: https://doi.org/10.29296/25877313-2025-02-01
- ID: 658375
Cite item
Abstract
Monoamine oxidase (MAO) is an FAD-dependent enzyme essential for regulating neurotransmitter levels and protecting the body from the harmful effects of amines. Dysregulated MAO activity, through either overexpression or excessive activation, has been linked to diverse pathological conditions. Emerging evidence highlights MAO as a key contributor to oxidative stress, driving significant damage not only to the nervous system but also to the cardiovascular system. Additionally, MAO is implicated in tumor progression and metastasis. Targeting MAO through chemical inhibition offers promising therapeutic avenues for treating neurodegenerative disorders, cancer, heart failure, rheumatoid arthritis, multiple sclerosis, and other inflammatory diseases. Potential applications also extend to addressing migraines, dizziness, attention deficit disorders, diabetes, obesity, muscular dystrophy, and metabolic dysfunctions. This review summarizes current methodologies for assessing MAO activity and inhibition, alongside in vivo models used to study neurodegenerative diseases, providing a foundation for future therapeutic strategies.
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About the authors
A. A. Romanycheva
Yaroslavl State Pedagogical University named after K.D. Ushinsky
Author for correspondence.
Email: kai-ren@yandex.ru
ORCID iD: 0000-0002-7931-1711
SPIN-code: 3994-4146
PhD (Biol.), Research Sciebtist, Department of Pharmaceutical Development, Center for Pharmaceutical Technology Transfer named after M.V. Dorogov
Russian Federation, Respublikanskaya street, 108/1, Yaroslavl, 150000V. N. Fedorov
Yaroslavl State Pedagogical University named after K.D. Ushinsky
Email: fedorov.vladimir@hotmail.com
ORCID iD: 0009-0003-1296-1861
SPIN-code: 4245-8787
Dr.Sc. (Med.), Professor, Head of the Pharmacological Research Departmen, Center for Pharmaceutical Technology Transfer named after M.V. Dorogov
Russian Federation, Respublikanskaya street, 108/1, Yaroslavl, 150000A. A. Shetnev
Yaroslavl State Pedagogical University named after K.D. Ushinsky
Email: a.shetnev@yspu.org
ORCID iD: 0000-0002-4389-461X
SPIN-code: 3410-7216
Ph.D. (Chem.), Head of the Pharmaceutical Development Department, Center for Pharmaceutical Technology Transfer named after M.V. Dorogov
Russian Federation, Respublikanskaya street, 108/1, Yaroslavl, 150000M. K. Korsakov
Yaroslavl State Pedagogical University named after K.D. Ushinsky
Email: mkkors@mail.ru
ORCID iD: 0000-0003-0913-2571
SPIN-code: 2897-2520
Dr.Sc. (Chem.), Associate Professor, Director Center for Pharmaceutical Technology Transfer named after M.V. Dorogov
Russian Federation, Respublikanskaya street, 108/1, Yaroslavl, 150000References
- Bhawna, Ashwani K., Meenakshi B. et al. Monoamine oxidase inhibitors: A concise review with special emphasis on structure activity relationship studies, European Journal of Medicinal Chemistry. 2022; 242: 114655; https://doi.org/10.1016/j.ejmech.2022.114655.
- Виноградов А.Д., Гривенникова В.Г. Генерация активных форм кислорода митохондриями. Успехи биологической химии. 2013; 53: 245–296. [Vinogradov A.D., Grivennikova V.G. Generation of reactive oxygen species by mitochondria. Advances in biological chemistry. 2013; 53: 245–296 (In Russ.)].
- Aljanabi R., Alsous L., Sabbah D.A. et al. Monoamine Oxidase (MAO) as a Potential Target for Anticancer Drug Design and Development. Molecules. 2021; 4; 26(19): 6019. doi: 10.3390/molecules26196019.
- Fabbri E., Balbi T., Canesi L. Neuroendocrine functions of monoamines in invertebrates: Focus on bivalve molluscs, Molecular and Cellular Endocrinology. 2024; 588, 112215; https://doi.org/10.1016/j.mce.2024.112215.
- Guthrie P.B., Neuhoff V., Osborne N.N. Monoamine oxidase activity in Helix pomatia. Experientia. 1975; 31: 775–776; https://doi.org/10.1007/BF01938457.
- Muellers S., Tararina M. Structural Insights into the Substrate Range of a Bacterial Monoamine Oxidase. Biochemistry. 2023; 62(3): 851–862. doi: 10.1007/BF01938457.
- Santema L., Basile L., Binda C., Fraaije M.W. Discovery and structural characterization of a thermostable bacterial monoamine oxidase. 2024; 291(5): 849–864; https://doi.org/10.1111/febs.16973.
- Мустафин Р.Н., Еникеева Р.Ф., Давыдова Ю.Д., Хуснутдинова Э.К. Роль эпигенетических факторов в развитии депрессивных расстройств. Генетика. 2018; 5412): 376–1389. [Mustafin R.N., Enikeeva R.F., Davydova Yu.D., Xusnutdinova E.A. The role of epigenetic factors in the development of depressive disorders. Genetics. 2018; 54(12): 376–1389. (In Russ.)].
- Andrews P.W., Bosyj C., Brenton L. et al. All the brain's a stage for serotonin: the forgotten story of serotonin diffusion across cell membranes. Proc Biol Sci. 2022 Nov 9; 289(1986): 20221565; http://doi.org/10.1098/rspb.2022.1565.
- Santin М., Resta М., Parini М., Mialet-Perez J. Monoamine oxidases in age-associated diseases. Ageing Res. Rev. 2021; 66: 101256; https://doi.org/10.1016/j.arr.2021.101256.
- Yeung A., Georgieva M.G., Atanasov A.G., Tzvetkov N.T. Monoamine Oxidases as Privileged Molecular Targets in Neuroscience: Research Literature Analysis, Front. Mol. Neurosci. 2019; 12:143; https://doi.org/10.3389/fnmol.2019.00143.
- Antonucci S., Di Sante M., Tonolo F. et al. The Determining Role of Mitochondrial Reactive Oxygen Species Generation and Mo-noamine Oxidase Activity in Doxorubicin-Induced Cardiotoxicity. 2021; 34(7): 531–550; https://doi.org/10.1089/ars.2019.7929.
- Xiaoya Wang, Xiaolei Song, Peng Li et al. Fluorescence method for monoamine oxidase B detection based on the cage function of glyoxal and phenethylamine on G-rich DNA, Sensors and Actuators B: Chemical. 2022; 372: 132624; https://doi.org/10.1016/j.snb.2022.132624.
- Alborghetti M., Bianchini E. et al. Type-B monoamine oxidase inhibitors in neurological diseases: clinical applications based on preclinical findings. Neural Regen. Res. 2024; 19(1):p 16-21. doi: 10.4103/1673-5374.375299.
- Куминский В.И. Увеличение ингибиторами моноаминоксидазы радиозащитного эффекта о-метилтирамина и мезатона. Радиобиология.1993; 33(1): 137–140. [Kuminsky V.I. Increase in inhibitors of the radioprotective effect of monoamine oxidase o-methyltyramine and mesatone. Radiobiology.1993; 33(1): 137–140. (In Russ.)].
- Ostadkarampour M., Putnins E.E. Monoamine Oxidase Inhibitors: A Review of Their Anti-Inflammatory Therapeutic Potential and Mechanisms of Action. Front. Pharmacol. 2021; 12: 676239. doi: 10.3389/fphar.2021.676239; https://doi.org/10.3389/fphar.2021.676239.
- Sur D., Mondal C., Balaraman A.K. et al. Attenuation of COX-2 enzyme by modulating H2O2-mediated NF-κB signaling pathway by monoamine oxidase inhibitor (MAOI): a further study on the reprofiling of MAOI in acute inflammation. Inflammopharmacol. 2023; 31: 1305–1317. doi: 10.1007/s10787-023-01165-5.
- Deshwal S., Di Sante M., Di Lisa F., Kaludercic N. Emerging role of monoamine oxidase as a therapeutic target for cardiovascular disease. Curr Opin Pharmacol. 2017 Apr; 33: 64–69. doi: 10.1016/j.coph.2017.04.003.
- Qiaoqiao Ci, Hong Yang, Yuanzhi Bian et al. An in situ fluorescent copolymer dots-based kit for the specific detection of monoamine oxidase-A in cell/tissue/human prostate cancer, Sensors and Actuators B: Chemical. 2023; 397: 134655; https://doi.org/10.1016/j.snb.2023.134655.
- Shih J.C. Monoamine oxidase isoenzymes: genes, functions and targets for behavior and cancer therapy. J Neural Transm. 2018; 125(11): 1553–1566. doi: 10.1007/s00702-018-1927-8.
- Wu J.B., Yin L., Shi C. et al. MAOA-Dependent Activation of Shh-IL6-RANKL Signaling Network Promotes Prostate Cancer Metastasis by Engaging Tumor-Stromal Cell Interactions. Cancer Cell. 2017; 13;31(3): 368–382. doi: 10.1016/j.ccell.2017.02.003.
- Yoshioka Y., Sugino Y., Shibagaki F. et al. Dopamine attenuates lipopolysaccharide-induced expression of proinfla-mmatory cytokines by inhibiting the nuclear translocation of NF-κB p65 through the formation of dopamine quinone in microglia. Eur. J. Pharmacol. 2020; 5; 866: 172826. doi: 10.1016/j.ejphar.2019.172826.
- Hanami K., Nakano K., Tanaka Y. Dopamine receptor signaling regulates human osteoclastogenesis. Nihon Rinsho Meneki Gakkai Kaishi. 2013; 36(1): 35–39. Japanese. doi: 10.2177/jsci.36.35. PMID: 23445730.
- Jenei-Lanzl Z., Capellino S., Kees F. et al. Anti-inflammatory effects of cell-based therapy with tyrosine hydroxylase-positive catecholaminergic cells in experimental arthritis. Ann Rheum Dis. 2015; 74(2): 444–4451. doi: 10.1136/annrheumdis-2013-203925.
- Rybaczyk L.A., Bashaw M.J., Pathak D.R. et al. An indicator of cancer: downregulation of Monoamine Oxidase-A in multiple organs and species. BMC Genomics. 2008; 9: 134; https://doi.org/10.1186/1471-2164-9-134.
- Li J., Yang X.-M., Wang, Y.-H. et al. Monoamine oxidase A suppresses hepatocellular carcinoma metastasis by inhibiting the adrenergic system and its transactivation of EGFR signaling. J. Hepatol. 2014; 60: 1225–1234; https://doi.org/10.1016/j.jhep.2014.02.025.
- Vitiello L., Marabita M., Sorato E. et al. Drug Repurposing for Duchenne Muscular Dystrophy. Front. Physiol. 2018; 9: 1087. doi: 10.3389/fphys.2018.01087.
- Tan Y.Y., Jenner P., Chen S.D. Monoamine oxidase-B inhibitors for the treatment of Parkinson’s disease: Past, present, and future. J. Parkinsons Dis. 2022; 12: 477–493. doi: 10.3233/JPD-212976.
- Murugan N.A., Zaleśny R. Multiscale modeling of two-photon probes for Parkinson’s diagnostics based on monoamine oxidase B biomarker J. Chem. Inf. Model. 2020; 60(8): 3854–3863; https://doi.org/10.1021/acs.jcim.0c00423.
- Zhang A., Yang X., Su. K. et al. The intracellular monoamine oxidase-A inhibitory activity and the protective effect of small hairtail-related peptides in nerve cells (SH-SY5Y), Bioscience, Biotechnology, and Biochemistry. 2024; 88(3): 322–332; https://doi.org/10.1093/bbb/zbad176.
- Медянцева Э.П., Варламова Р.М., Гималетдинова Д.А. и др. Условия функционирования амперометрического био-сенсора на основе моноаминоксидазы. Ученые записки Казанского госуниверситета. 2006; 148(2): 21–29. [Medyantseva E.P., Varlamova R.M., Gimaletdinova D.A. i dr. Operating conditions of an amperometric biosensor based on monoamine oxidase. Scientific notes of Kazan State University. 2006; 148(2): 21–29. (In Russ.)].
- Хохлов А.Л., Яичков И.И., Корсаков М.К. и др. Разработка и валидация методики количественного определения моноаминовых нейромедиаторов и их метаболитов в тканях мозга крыс с помощью ВЭЖХ-МС/МС. Acta biomedica scientifica. 2024; 9(1): 177–191. [Khokhlov A.L., Yaichkov I.I., Korsakov M.K. i dr. Development and validation of a method for the quantitative determination of monoamine neurotransmitters and their metabolites in rat brain tissue using HPLC-MS/MS. Acta biomedica scientifica. 2024; 9(1): 177–191. (In Russ.)]. doi: 10.29413/ABS.2024-9.1.18.
- Shetnev A.A., Efimova J.A., Korsakov M.K. et al. Synthesis and Monoamine Oxidase Inhibition Properties of 4-(2-Methyloxazol-4-yl)benzenesulfonamide. Molbank. 2024; M1787; https://doi.org/10.3390/M1787.
- Tipton K.F., Davey G., Motherway M. Monoamine oxidase assays. Current Protocols in Pharmacology. 2001 May; Chapter 3: Unit3.6. doi: 10.1002/0471141755.ph0306s09.
- Li H., Luo W., Lin J. et al. Assay of plasma semicarbazide-sensitive amine oxidase and determination, Journal of Chromatography B. 2004; 810(2): 277–282; https://doi.org/10.1016/j.jchromb.2004.08.011.
- Weiss H.G, Klocker J., Labeck B. et al. Plasma amine oxidase: a postulated cardiovascular risk factor in nondiabetic obese patients. Metabolism. 2003; 52(6): 688–692; https://doi.org/10.1016/S0026-0495(03)00028-3.
- Schwelberger H.G., Feurle J. Luminometric determination of amine oxidase activity.Inflamm. res. 2007; 56: S53–S54; https://doi.org/10.1007/s00011-006-0526-6.
- Monoamine Oxidase A (MAO-A) Inhibitor Screening Kit (Fluorometric) (MAK295). Technical Bulletin. 2024. Sigma-Aldrich. 3 p.
- Kaya B., Yurttaş L., Sağlik B. et al. Novel 1-(2-pyrimidin-2-yl)piperazine derivatives as selective monoamine oxidase (MAO)-A inhibitors.Journal of Enzyme Inhibition and Medicinal Chemistry. 2017; 32(1); 193–202; https://doi.org/10.1080/14756366.2016.1247054.
- Ling K.Q., Sayre L.M. Sayre Discovery of a Sensitive, Selective, and Tightly Binding Fluorogenic Substrate of Bovine Plasma Amine Oxidase J. Org. Chem. 2009; 74(1): 339–350; https://doi.org/10.1021/jo8018945.
- Воронков Д.Н., Худоерков Р.М., Доведова Е.Л. Изменения нейроглиального взаимодействия в нигростриатных структурах мозга при моделировании дисфункции дофаминовой системы. Журнал неврологии и психиатрии им. C.C. Корсакова. 2013; 113(7): 47–55. [Voronkov D.N., Hudoerkov R.M., Dovedova E.L. Izmeneniya nejroglial'nogo vzaimo-dejstviya v nigrostriatnyh strukturah mozga pri modelirovanii disfunkcii dofaminovoj sistemy. Zhurnal nevrologii i psihiatrii im. C.C. Korsakova. 2013; 113(7): 47–55. (In Russ.)].
- Mergemeier K., Lehr M. HPLC-UV assays for evaluation of inhibitors of mono and diamine oxidases using novel phenyltetrazolylalkanamine substrates. Anal Biochem. 2018; 15: 549: 29–38. doi: 10.1016/j.ab.2018.03.007.
- Sblano S., Boccarelli A., Mesiti F. et al. A second life for MAO inhibitors? From CNS diseases to anticancer therapy. European Journal of Medicinal Chemistry. 2024; 267.
- Monoamine Oxidase B Inhibitor Screening Kit (Fluorometric) (MAK296). Technical Bulletin. 2024. Sigma-Aldrich. 3 p.
- Love A., Prescher A. Seeing (and using) the Light: Recent Developments in Bioluminescence Technology, Cell Chemical Biology, 2020; 27(8): 904–920.
- Басова И.Н., Ягодина О.В. Особенности энзимологических свойств моноаминоксидазы печени ладожского кольчатого тюленя. Актуальные вопросы ветеринарной биологии. 2013; 2(18): 30–37. [Basova I.N., Yagodina O.V. Features of enzymological properties of monoamine oxidase from the liver of the Ladoga ringed seal. Actual issues of veterinary biology. 2013; 2(18): 30–37. (In Russ.)].
- Gwynne W.D., Shakeel M.S., Wu J. et al. Monoamine oxidase-A activity is required for clonal tumorsphere formation by human breast tumor cells. Cell Mol Biol Lett. 2019; 24: 59; https://doi.org/10.1186/s11658-019-0183-8.
- Мельникова Е.В., Меркулов В.А., Меркулова О.В. Генная терапия нейродегенеративных заболеваний: достижения, разработки, проблемы внедрения в клиническую практику. БИОпрепараты. Профилактика, диагностика, лечение. 2023; 23(2): 127–147. [Melnikova E.V., Merkulov V.A., Merkulova O.V. Gene therapy for neurodegenerative diseases: achievements, developments, problems of implementation in clinical practice. BIOpreparations. Prevention, diagnosis, treatment. 2023; 23(2): 127–147. (In Russ.)]; https://doi. org/10.30895/2221-996X-2023-433.
- Козина Е.А., Колачева А.А., Кудрин В.С. и др. Хронические модели доклинической и ранней клинической стадий болезни Паркинсона на мышах. 2016; Нейрохимия. 33(3): 222–229. [Kozina E.A., Kolacheva A.A., Kudrin V.S. i dr. Chronic models of preclinical and early clinical stages of Parkinson’s disease in mice. Neurochemistry. 2016; 33(3): 222–229. (In Russ.)]. doi: 10.7868/S1027813316030092.
- Nordio G., Piazzola F., Cozza G. et al. From Monoamine Oxidase Inhibition to Antiproliferative Activity: New Biological Perspectives for Polyamine Analogs. Molecules. 2023; 29; 28(17): 6329. doi: 10.3390/molecules28176329.
- Kumar S., Oh J.M., Prabhakaran P. et al. Isatin-tethered halogen-containing acylhydrazone derivatives as monoamine oxidase inhibitor with neuroprotective effect. Sci Rep. 2024; 14: 1264; https://doi.org/10.1038/s41598-024-51728-x.
- Esther del Olmo, Bianca Barboza, Maria Delgado-Esteban. Potent, selective and reversible hMAO-B inhibition by benzalphthalides: Synthesis, enzymatic and cellular evaluations and virtual docking and predictive studies, Bioorganic Chemistry. 2024; 146: 107255; https://doi.org/10.1016/j.bio-org.2024.107255.
- Zhao H., Nolley R., Chen Z. Inhibition of monoamine oxidase A promotes secretory differentiation in basal prostatic epithelial cells. Differentiation. 2008; 76(7): 820–830. doi: 10.1111/j.1432-0436.2007.00263. x.
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