Progress in monoamine oxidase (MAO)
research in relation to genetic engineering

by
Nagatsu T.
Institute for Comprehensive Medical Science,
Fujita Health University,
Toyoake, Aichi 470-1192, Japan.
tnagatsu@fujita-hu.ac.jpia,
1985 Zonal Ave,
Los Angeles, CA 90033, USA.
jcshih@usc.edu
Neurotoxicology. 2004 Jan;25(1-2):11-20.


ABSTRACT

Monoamine oxidase (MAO) is an enzyme that oxidizes various physiologically and pathologically important monoamine neurotransmitters and hormones such as dopamine, noradrenaline, adrenaline, and serotonin. Two types of MAO, i.e. type A (MAO-A) and type B (MAO-B), were first discovered pharmacologically. MAO-A is inhibited by clorgyline; and MAO-B, by deprenyl. cDNAs MAO-A and MAO-B were cloned and their structures determined. MAO-A and MAO-B are made of similar but different polypeptides and encoded by different nuclear genes located on the X chromosome (Xp11.23). MAO-A and MAO-B genes consist of 15 exons with identical intron-exon organization, suggesting that they were derived from a common ancestral gene. Both enzymes require a flavin cofactor, flavin adenine dinucleotide (FAD), which binds to the cysteine residue of a pentapeptide sequence (Ser-Gly-Gly-Cys-Tyr). Both enzymes exist on the outer membrane of mitochondria of various types of cells in various tissues including the brain. In humans, MAO-A is abundant in the brain and liver, whereas the liver, lungs and intestine are rich in MAO-B. MAO-A oxidizes noradrenaline and serotonin; and MAO-B, mainly beta-phenylethylamine. In the human brain, MAO-A exists in catecholaminergic neurons, but MAO-B is found in serotonergic neurons and glial cells. MAO-A knockout mice exhibit increased serotonin levels and aggressive behavior, whereas MAO-B knockout mice show little behavioral change. The gene knockout mice of MAO-A or MAO-B, together with the observation that some humans lack MAO-A, MAO-B, or both have contributed to our understanding of the function of MAO-A and MAO-B in health and disease. MAO-A and MAO-B may be closely related to various neuropsychiatric disorders such as depression and Parkinson's disease, and inhibitors of them are the subject of drug development for such diseases.


MAOIs
Rasagiline
Neuroprotection
Rasagiline: structure
MAO-b inhibitors/PD
Anti-apoptotic activity
Molecular mechanisms
Rasagiline pharmacology
Induction of pro-survival genes
Rasagiline and the mitochondria
Antioxidant strategies against aging
Anti-Alzheimer/anti-Parkinson's drugs
Rasagiline versus selegiline metabolites
Rasagiline/ anti-apoptotic bcl-2 gene family
Dual AChE and MAO inhibitors and Alzheimer's
Rasagiline v selegiline: neuronal survival effects
Rasagiline (Agilect) in early Parkinson's disease


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