MAO-B

Monoamine oxidase B (MAO-B) is a mitochondrial enzyme responsible for the oxidative deamination of monoamine neurotransmitters, including dopamine and β-phenylethylamine, contributing to the regulation of synaptic neurotransmission^[1][2]. Mechanistically, MAO-B generates reactive oxygen species (ROS) during substrate metabolism, which can influence oxidative stress and mitochondrial function in neurons^[3][4]. Compared with MAO-A, MAO-B expression increases with aging and is particularly prominent in glial cells, establishing its distinct role in neurodegenerative processes^[5][6]. In Parkinson’s disease models, elevated MAO-B activity in the substantia nigra pars compacta leads to dopamine depletion and motor deficits, making selective MAO-B inhibition a validated therapeutic strategy^[7][8]. Selective inhibitors, including selegiline and rasagiline, bind covalently to the flavin adenine dinucleotide cofactor, irreversibly inactivating MAO-B while sparing MAO-A, which minimizes peripheral tyramine interactions^[9][10]. Recent drug design efforts exploit structural scaffolds such as propargylamines, coumarin-pyridazine hybrids, and 2-phenylbenzofurans, achieving submicromolar potency, isoform selectivity, and favorable blood-brain barrier penetration^[11][12][13]. For experimental applications, these inhibitors are used both as pharmacological tools to probe MAO-B function and as lead compounds in preclinical models of Parkinson’s and Alzheimer’s diseases^[14][10]. Structural variations, such as β-methylation and para-substitutions on the aromatic ring, modulate binding conformation and substrate/inhibitor specificity within the MAO-B active site^[15].