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1. Introduction
Monoamine oxidase (MAO) catalyzes the oxidative deamination of biogenic and xenobiotic amines and has an important role in the metabolism of neuroactive and vasoactive amines in the central nervous system (CNS) and peripheral tissues. The enzyme preferentially degrades benzylamine and phenylethylamine and targets a wide variety of specific neurotransmitters involved in the primary substrates of MAO in the brain, including epinephrine (EP), norepinephrine (NE), dopamine (DA), serotonin (5-HT), and β-phenylethylamine (PEA) (1,2). The unique position of MAO in modulating the function of a diverse series of specific neurotransmitters in association with various conditions, including mood disorders (3), anxiety and depression (4,5), schizophrenia (6), attention deficit hyperactivity disorder (7–9), migraine (10), sexual maturation (11) and neurodegenerative diseases (12), has attracted significant attention to the protein as a therapeutic target.
Compelling studies have shown that the involvement of MAO in AD and neurodegenerative diseases plays an important role in several key pathophysiological mechanisms (13,14). MAO-B has been proposed as a biomarker, whereas activated MAO-B leads to cognitive dysfunction, destroys cholinergic neurons, causes disorder of the cholinergic system and contributes to the formation of amyloid plaques.
The present review focused on evidence supporting the central role that MAO has in AD pathogenesis, including the formation of amyloid plaques from amyloid β peptide (Aβ) production and neurofibrillary tangles (NFTs), and cognitive impairment via the destruction of cholinergic neurons and disorder of the cholinergic system. Studies reporting that MAO inhibitors improve cognitive deficits and reverse Aβ pathology by modulating proteolytic cleavage of amyloid precursor protein (APP) and decreasing Aβ protein fragments are also discussed. Finally, on the basis of current advances in the use of MAO inhibitors for the treatment of AD, MAO inhibitors are discussed as a promising therapeutic target for AD.
2. MAO
Monoamine oxidase (EC1.4.3.4, a flavin-containing enzyme) is widely distributed in animal tissue and catalyzes the oxidative deamination of primary amines by reaction between dioxygen and R-CH2-NH2 to form R-CHO, NH3 and H2O2 (Fig. 1). MAO removes an amine group by catalyzing the oxidative deamination of monoamines, resulting in the corresponding aldehyde and ammonia. MAO exists as two isozymes in humans: MAO-A and MAO-B, which are distinct due to different amino acid sequences, three-dimensional structures, distributions...