Cloning, after cloning, knock-out mice,
and physiological functions of MAO A and B

by
Shih JC.
Department of Molecular Pharmacology and Toxicology,
Pharmaceutical Science Center,
University of Southern California,
1985 Zonal Ave,
Los Angeles, CA 90033, USA.
jcshih@usc.edu
Neurotoxicology. 2004 Jan;25(1-2):21-30.


ABSTRACT

Cloning of MAO A and B has demonstrated clearly that MAO A and B are coded by different proteins with 70% amino acid identity. With the MAO A and B cDNA clones, we showed the tissue distribution and genomic structure of MAO A and B, the latter suggesting that they are derived from the same ancestral gene. The active sites, the role of cysteine residues, the three-dimensional models and the mitochondria targeting domains of both isoenzymes have been established. The transcriptional regulation of MAO A and B has been studied. MAO A KO mice showed increased levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) whereas MAO B KO mice showed increased phenylethylamine (PEA) levels only. Both MAO A and B KO mice showed increased response to stress. MAO A KO mice showed increased emotional learning and memory and aggressive behavior, but the vesicular monoamine transporter (VMAT2), 5-HT1A, 5-HT2A and 5-HT2C receptors were down regulated. 5-HT2A antagonist, ketanserin and MDL100907 were able to abolish the aggression, suggesting that the aggressive behavior may be mediated by 5-HT2A receptor. In contrast, MAO B KO mice are resistant to MPTP, a toxin which induces Parkinson's syndromes. Studies of these mice suggest that MAO A and B have distinct biochemical and physiological functions.


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
MAO research and genetic engineering


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