Monoamine oxidase as a target for the development of new drugs

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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, 150000

V. 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, 150000

A. 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, 150000

M. 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, 150000

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Supplementary files

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2. Fig. 1. Structural similarity of monoamine oxidase from Thermoanaerobacterales bacterium (A) with other eukaryotic MAOs (B) [7]

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3. Fig. 2. IC₅₀ (μM) of compound 2j MAO-A inhibitor [39]

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4. Fig. 3. 2D (A) and 3D (B) Cell Culture Models [50]

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5. Fig. 4. Monoamine oxidase A (MAO-A) expression in normal human prostate epithelial (E-PZ) and stromal (F-PZ) cells: MAO-A protein is readily detectable in E-PZ cells by Western blotting, while little or no MAO-A protein can be measured in F-PZ cells (A);Expression pattern of proteins of interest in E-PZ cells by immunocytochemistry – MAOA (B), K14 (C), p63(D), K18 (E), AR (F), Ki67 (G) [53]

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