Monoamine oxidase B
About: Monoamine oxidase B is a(n) research topic. Over the lifetime, 2698 publication(s) have been published within this topic receiving 86759 citation(s). The topic is also known as: Monoamine oxidase B.
Papers published on a yearly basis
TL;DR: The hypothesis that in the enzyme prepared, the MAO is a binary system of enzymes each of which has a detectably different sensitivity to this particular inhibitor, is put forward and evidence after dialysis supports this hypothesis.
Abstract: The inhibition of monoamine oxidase (MAO) in vitro and in vivo by N-methyl-N-propargyl-3(2,4-dichlorophenoxy) propylamine hydrochloride (M&B 9302) is described. The kinetics of the MAO-M&B 9302 reaction show a unique abnormality as compared with known inhibitors. The plot of percentage inhibition against concentration of M&B 9302 does not show a simple sigmoid curve, but reveals a pair of sigmoid curves joined by a horizontal section where the inhibition is invariant. The hypothesis that in the enzyme prepared, the MAO is a binary system of enzymes each of which has a detectably different sensitivity to this particular inhibitor, is put forward and discussed. Evidence after dialysis supports this hypothesis.
TL;DR: Blockage of dopamine uptake by mazindol prevents MPTP-induced damage to nigrostriatal dopamine neurons, indicating that MPP+ concentration into dopamine neurons explains their selective destruction by MPTP.
Abstract: N-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces neuropathological and clinical abnormalities in humans, monkeys, and mice that closely resemble idiopathic parkinsonism. N-Methyl-4-phenylpyridine (MPP+), a metabolite of MPTP formed by monoamine oxidase B, is accumulated into striatal and cerebral cortical synaptosomes by the dopamine and norepinephrine uptake systems, respectively, whereas MPTP itself is not accumulated. The potencies of drugs in inhibiting [3H]MPP+ or [3H]dopamine uptake into striatal synaptosomes are very similar, as are potencies in inhibiting [3H]MPP+ or [3H]norepinephrine uptake into cortical synaptosomes. The Km values for [3H]MPP+ uptake are 170 and 65 nM and the Vmax values are 2 and 0.1 nmol/g of tissue per min in rat striatum and cortex, respectively, similar to values for [3H]dopamine uptake, Autoradiography of accumulated [3H]MPP+ in slices of rat brain shows high densities in the caudate-putamen and nucleus accumbens. Furthermore, blockade of dopamine uptake by mazindol prevents MPTP-induced damage to nigrostriatal dopamine neurons, indicating that MPP+ concentration into dopamine neurons explains their selective destruction by MPTP.
TL;DR: A new polymorphism upstream of the gene for monoamine oxidase A, which consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies, may be useful as both a functional and an anonymous genetic marker for MAOA.
Abstract: We describe a new polymorphism upstream of the gene for monoamine oxidase A (MAOA), an important enzyme in human physiology and behavior. The polymorphism, which is located 1.2 kb upstream of the MAOA coding sequences, consists of a 30-bp repeated sequence present in 3, 3.5, 4, or 5 copies. The polymorphism is in linkage disequilibrium with other MAOA and MAOB gene markers and displays significant variations in allele frequencies across ethnic groups. The polymorphism has been shown to affect the transcriptional activity of the MAOA gene promoter by gene fusion and transfection experiments involving three different cell types. Alleles with 3.5 or 4 copies of the repeat sequence are transcribed 2–10 times more efficiently than those with 3 or 5 copies of the repeat, suggesting an optimal length for the regulatory region. This promoter region polymorphism may be useful as both a functional and an anonymous genetic marker for MAOA.
TL;DR: MAO A and B knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders and show increased reactivity to stress.
Abstract: Cloning of MAO (monoamine oxidase) A and B has demonstrated unequivocally that these enzymes are made up of different polypeptides, and our understanding of MAO structure, regulation, and function has been significantly advanced by studies using their cDNA. MAO A and B genes are located on the X-chromosome (Xp11.23) and comprise 15 exons with identical intron-exon organization, which suggests that they are derived from the same ancestral gene. MAO A and B knock-out mice exhibit distinct differences in neurotransmitter metabolism and behavior. MAO A knock-out mice have elevated brain levels of serotonin, norephinephrine, and dopamine and manifest aggressive behavior similar to human males with a deletion of MAO A. In contrast, MAO B knock-out mice do not exhibit aggression and only levels of phenylethylamine are increased. Mice lacking MAO B are resistant to the Parkinsongenic neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine. Both MAO A and B knock-out mice show increased reactivity to stress. These knock-out mice are valuable models for investigating the role of monoamines in psychoses and neurodegenerative and stress-related disorders.
TL;DR: It is reported that pargyline, nialamide and tranylcypromine, which inhibit both MAO-A andMAO-B, when administered to mice before MPTP, protect against MPTP-induced dopaminergic neurotoxicity.
Abstract: 1-Methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) causes degeneration of the dopaminergic nigrostriatal pathway in several animal species, including humans1,2, monkeys3,4 and mice5–7. Changes observed after MPTP administration include marked decrements in the neostriatal content of dopamine and its major metabolites, dihydroxyphenylacetic acid and homovanillic acid, and a greatly diminished capacity of neostriatal synaptosomes to take up 3H-dopamine5,6. In contrast, there is no pronounced loss of serotonin in the neostriatum or of dopamine and its metabolites in other brain areas in MPTP-treated animals. The oxidative metabolism of MPTP to 1-methyl-4-phenyl pyridine, a positively charged species, has been suggested as a critical feature in the neurotoxic process8. Moreover, in rat brain preparations, the monoamine oxidase (MAO) inhibitor pargyline and the specific MAO-B inhibitor deprenil can prevent the formation of 1-methyl-4-phenyl-pyridine from MPTP, while the specific MAO-A inhibitor clorgyline has no such effect9, suggesting that MAO, and specifically MAO-B, is responsible for the oxidative metabolism of MPTP. We now report that pargyline, nialamide and tranylcypromine, which inhibit both MAO-A and MAO-B, when administered to mice before MPTP, protect against MPTP-induced dopaminergic neurotoxicity. Deprenil is also protective, but clorgyline is not. Our data are consistent with the premise that MAO-B has a crucial role in MPTP-induced degeneration of the nigrostriatal dopaminergic neuronal pathway.