Monoamine Oxidase-B (MAO-B) Inhibitors in the Treatment of Alzheimer’s and Parkinson’s Disease

Abstract

Background: The MAO enzyme which is presented in the brain and peripheral tissues and is a significant enzyme that is responsible for the deamination of biogenic amines and thus regulation of neurotransmitter levels. The reaction of these neurotransmitters with MAO enzyme produces aldehyde and free amine. MAO enzyme consists of two isoforms, MAO-A and MAO-B, which are characterized by amino acid sequence, three-dimensional structure, substrate preference and inhibitor selectivity. Dopamine, tyramine, and tryptamine are substrates of both MAO isoforms and MAO inhibitors such as clorgiline, selegiline that are used as medications in neurodegenerative and neurological diseases. In particular, MAO-A inhibitors are used in the treatment of depression, while MAO-B inhibitors are used in the treatment of Parkinson's disease. It is also investigated whether MAO-B inhibitors are effective in the treatment of Alzheimer's disease. Nowadays, life expectancy has increased; as a result, neurodegenerative diseases such as Parkinson's and Alzheimer's disease have started to seen more frequently. The elderly population is increasing day by day. As a result of these common diseases in the elderly people, these people are unable to do their jobs and need care. Therefore, these diseases have become a significant health problem in society. Methods: In this study, review, inclusion and exclusion criteria were used. Research articles with peer-reviewed were searched. The quality of the examined articles was evaluated with standard tools. The information obtained was analyzed conceptually by using qualitative content analysis methodology. Results: One hundred and five papers were included in the review. The current MAO-B inhibitors and their usage areas are discussed together with the structures of the drugs; also, their possible effects in Alzheimer’s and Parkinson’s treatment are evaluated. In addition, different articles have been compiled in which structures such as arylalkylamines, chalcones, benzoquinone, benzoxazinone, chromen are substituted with various functional groups and aromatic rings, and structures of 44 different compounds that have recently been developed and their inhibitory effects on MAO-B enzyme. As a result, the structure required for MAO-B inhibition and SAR studies are discussed and the literature was shed light. Conclusion: Many studies demonstrate that MAO-B activity increases with age in brain tissue, cerebrospinal fluid (CSF), and platelets in Alzheimer's patients. This suggests that MAO-B inhibitor drugs, which may be effective in the treatment of Parkinson's disease, may also be effective in the treatment of Alzheimer's disease. This article was written to explain the multifaceted MAO-B inhibitor molecules.

Roles of selected non-P450 human oxidoreductase enzymes in protective and toxic effects of chemicals: review and compilation of reactions

“…At present, drugs that are inhibitors of MAO A are used and investigated for the treatment of depression, while selective MAO B inhibitors (e.g., rasagiline, selegiline), are used in the treatment of Parkinson's disease, avoiding severe side effects. It has been suggested that MAO B inhibitor drugs might be effective in the treatment of Alzheimer’s disease (Finberg 2014 ; Özdemir et al 2021 ; Shulman et al 2013 ; Szökő et al 2018 ; Yamada and Yasuhara 2004 ; Youdim 1975 ; Youdim and Bakhle 2006 ).…”

CADMA-Chem: A Computational Protocol Based on Chemical Properties Aimed to Design Multifunctional Antioxidants

“…While there are currently no therapies that prevent or slow down PD and AD [ 65 ], some progress has been made to alleviate the symptoms. Acetylcholinesterase (AChE) inhibitors are used as symptomatic therapies for AD [ 26 , 66 , 67 ], while catechol-O-methyl transferase (COMT) [ 68 , 69 , 70 , 71 ] and monoamine oxidase B (MAOB) [ 72 , 73 , 74 , 75 ] inhibitors are used for PD. In addition, antioxidant-based therapies are emerging as promising complements since they improve neurocognitive performances and prevent excessive neuronal loss [ 50 ].…”

Development of a Novel Class of Pyridazinone Derivatives as Selective MAO-B Inhibitors

“…As a corollary, adopting MAO-B inhibitors in the initial phases of the disease may postpone the emergence of significant symptoms and the necessity for L-dopa. [7].…”