Monoamine oxidase and neurodegeneration: Mechanisms, inhibitors and natural compounds for therapeutic intervention.

Autor: Banerjee C; Cell Biology and Physiology Division, CSIR- Indian Institute of Chemical Biology, Kolkata, 700032, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India., Tripathy D; Department of Zoology, Netaji Nagar College for Women, Kolkata, 700092, India., Kumar D; Organic and Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700032, India. Electronic address: deepak@iicb.res.in., Chakraborty J; Cell Biology and Physiology Division, CSIR- Indian Institute of Chemical Biology, Kolkata, 700032, India. Electronic address: joy.chakraborty@iicb.res.in.
Jazyk: angličtina
Zdroj: Neurochemistry international [Neurochem Int] 2024 Oct; Vol. 179, pp. 105831. Date of Electronic Publication: 2024 Aug 14.
DOI: 10.1016/j.neuint.2024.105831
Abstrakt: Mammalian flavoenzyme Monoamine oxidase (MAO) resides on the outer mitochondrial membrane (OMM) and it is involved in the metabolism of different monoamine neurotransmitters in brain. During MAO mediated oxidative deamination of relevant substrates, H 2 O 2 is released as a catalytic by-product, thus serving as a major source of reactive oxygen species (ROS). Under normal conditions, MAO mediated ROS is reported to propel the functioning of mitochondrial electron transport chain and phasic dopamine release. However, due to its localization onto mitochondria, sudden elevation in its enzymatic activity could directly impact the form and function of the organelle. For instance, in the case of Parkinson's disease (PD) patients who are on l-dopa therapy, the enzyme could be a concurrent source of extensive ROS production in the presence of uncontrolled substrate (dopamine) availability, thus further impacting the health of surviving neurons. It is worth mentioning that the expression of the enzyme in different brain compartments increases with age. Moreover, the involvement of MAO in the progression of neurological disorders such as PD, Alzheimer's disease and depression has been extensively studied in recent times. Although the usage of available synthetic MAO inhibitors has been instrumental in managing these conditions, the associated complications have raised significant concerns lately. Natural products have served as a major source of lead molecules in modern-day drug discovery; however, there is still no FDA-approved MAO inhibitor which is derived from natural sources. In this review, we have provided a comprehensive overview of MAO and how the enzyme system is involved in the pathogenesis of different age-associated neuropathologic conditions. We further discussed the applications and drawbacks of the long-term usage of presently available synthetic MAO inhibitors. Additionally, we have highlighted the prospect and worth of natural product derived molecules in addressing MAO associated complications.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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