Showing papers on "Monoamine oxidase B published in 2008"

Structure of human monoamine oxidase A at 2.2-A resolution: The control of opening the entry for substrates/inhibitors

Abstract: The mitochondrial outer membrane-anchored monoamine oxidase (MAO) is a biochemically important flavoenzyme that catalyzes the deamination of biogenic and xenobiotic amines Its two subtypes, MAOA and MAOB, are linked to several psychiatric disorders and therefore are interesting targets for drug design To understand the relationship between structure and function of this enzyme, we extended our previous low-resolution rat MAOA structure to the high-resolution wild-type and G110A mutant human MAOA structures at 22 and 217 A, respectively The high-resolution MAOA structures are similar to those of rat MAOA and human MAOB, but different from the known structure of human MAOA [De Colibus L, et al (2005) Proc Natl Acad Sci USA 102:12684-12689], specifically regarding residues 108-118 and 210-216, which surround the substrate/inhibitor cavity The results confirm that the inhibitor selectivity of MAOA and MAOB is caused by the structural differences arising from Ile-335 in MAOA vs Tyr-326 in MAOB The structures exhibit a C-terminal transmembrane helix with clear electron density, as is also seen in rat MAOA Mutations on one residue of loop 108-118, G110, which is far from the active center but close to the membrane surface, cause the solubilized enzyme to undergo a dramatic drop in activity, but have less effect when the enzyme is anchored in the membrane These results suggest that the flexibility of loop 108-118, facilitated by anchoring the enzyme into the membrane, is essential for controlling substrate access to the active site We report on the observation of the structure-function relationship between a transmembrane helical anchor and an extra-membrane domain

MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Abstract: Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing.

Inhibition of monoamine oxidase-B by the polyphenolic compound, curcumin and its metabolite tetrahydrocurcumin, in a model of Parkinson's disease induced by MPTP neurodegeneration in mice.

Abstract: We investigated the effects of the polyphenolic compound curcumin and its metabolite tetrahydrocurcumin (ThC), in the model of Parkinson's disease induced in mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this model depletion of dopamine(DA) and DOPAC (3,4-dihydroxy phenyl acetic acid)) occurs with increased monoamine oxidase (MAO-B) activity. We used HPLC with electrochemical detection to measure DA and DOPAC respectively while MAO-B was assayed by spectroflourimetry using the conversion of the fluorogenic substrate, kyuramine. Systemic administration of curcumin (80 mg/kg i. p.) and tetrahydrocurcumin (60 mg/kg i. p.) significantly reversed the MPTP-induced depletion of DA and DOPAC. The MAO-B activity was also significantly inhibited by these compounds. The results showed that curcumin and tetrahydrocurcumin reversed the MPTP induced depletion of DA and DOPAC which may in part be due to inhibition of MAO-B activity. In conclusion, both curcumin and its metabolite ThC exert neuroprotection against MPTP induced neurotoxicity.

The PPARγ agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B

Abstract: Background and purpose: The peroxisome proliferator-activated receptor-g (PPARg) agonist pioglitazone has previously been shown to attenuate dopaminergic cell loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease, an effect attributed to its anti-inflammatory properties. In the present investigation, we provide evidence that pioglitazone is effective in the MPTP mouse model, not via an anti-inflammatory action, but through inhibition of MAO-B, the enzyme required to biotransform MPTP to its active neurotoxic metabolite 1-methyl-4-phenylpyridinium (MPP þ ). Experimental approach: Mice were treated with pioglitazone (20 mg kg � 1 b.i.d. (twice a day), p.o., for 7 days), prior and post or post-MPTP (30 mg kg � 1 s.c.) treatment. Mice were then assessed for motor impairments on a beam-walking apparatus and for reductions in TH immunoreactivity in the substantia nigra and depletions in striatal dopamine. The effects of pioglitazone on striatal MPP þ levels and MAO-B activity were also assessed. Key results: Mice treated with MPTP showed deficits in motor performance, marked depletions in striatal dopamine levels and a concomitant reduction in TH immunoreactivity in the substantia nigra. Pretreatment with pioglitazone completely prevented these effects of MPTP. However, pretreatment with pioglitazone also significantly inhibited the MPTP-induced production of striatal MPP þ and the activity of MAO-B in the striatum. Conclusions and implications: The neuroprotection observed with pioglitazone pretreatment in the MPTP mouse model was due to the blockade of the conversion of MPTP to its active toxic metabolite MPP þ , via inhibition of MAO-B. British Journal of Pharmacology (2008) 154, 226–233; doi:10.1038/bjp.2008.78; published online 10 March 2008

β-Phenylethylamine Alters Monoamine Transporter Function via Trace Amine-Associated Receptor 1: Implication for Modulatory Roles of Trace Amines in Brain

Abstract: Brain monoamines include common biogenic amines (dopamine, norepinephrine, and serotonin) and trace amines [beta-phenylethylamine (beta-PEA), tyramine, tryptamine, and octopamine]. Common biogenic amines are well established as neurotransmitters, but the roles and functional importance of trace amines remain elusive. Here, we re-evaluated the interaction of trace amines with trace amine-associated receptor 1 (TAAR1) and investigated effects of beta-PEA on monoamine transporter function and influence of monoamine autoreceptors on TAAR1 signaling. We confirmed that TAAR1 was activated by trace amines and demonstrated that TAAR1 activation by beta-PEA significantly inhibited uptake and induced efflux of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin in transfected cells. In brain synaptosomes, beta-PEA significantly inhibited uptake and induced efflux of [3H]dopamine and [3H]serotonin in striatal and [3H]norepinephrine in thalamic synaptosomes of rhesus monkeys and wild-type mice, but it lacked the same effects in synaptosomes of TAAR1 knockout mice. The effect of beta-PEA on efflux was blocked by transporter inhibitors in either the transfected cells or wild-type mouse synaptosomes. We also demonstrated that TAAR1 signaling was not affected by monoamine autoreceptors at exposure to trace amines that we show to have poor binding affinity for the autoreceptors relative to common biogenic amines. These results reveal that beta-PEA alters monoamine transporter function via interacting with TAAR1 but not monoamine autoreceptors. The functional profile of beta-PEA may reveal a common mechanism by which trace amines exert modulatory effects on monoamine transporters in brain.

Synthesis, stereochemical identification, and selective inhibitory activity against human monoamine oxidase-B of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones.

Abstract: A series of 2-methylcyclohexylidene-(4-arylthiazol-2-yl)hydrazones have been investigated for their ability to inhibit selectively the activity of the human A and B isoforms of monoamine oxidase (MAO). The target compounds, which present a stereogenic center on the cyclohexane ring, were obtained as pure (R) and (S) enantiomers by enantioselective HPLC. The absolute configuration of homochiral forms isolated on a semipreparative scale was obtained by a combined strategy based on chemical correlation and single-crystal X-ray diffraction. All compounds showed higher activity against the human MAO-B isoform with IC50 values ranging between 26.81 +/- 2.74 microM and 14.20 +/- 0.26 nM, and the assays carried out on the pure enantiomers showed higher activity for the (R) form. A computational study was performed by molecular mechanics, DFT-based quantomechanics, and docking techniques on the most active and human MAO-B selective inhibitor 8.

Obesity is associated with genetic variants that alter dopamine availability.

Abstract: Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a well-characterized functional variant. Here we look at these four functional polymorphisms together, to investigate how heritable variation in dopamine levels influences the risk of obesity in a cohort of 1150, including 240 defined as obese (BMI > or = 30). The COMT and SLC6A3 polymorphisms showed no association with either weight, BMI or obesity risk. We found, however, that both MAOA and MAOB show an excess of the low-activity genotypes in obese individuals (MAOA:chi2= 15.45, p = 0.004; MAOB:chi2= 8.05, p = 0.018). Additionally, the MAOA genotype was significantly associated with both weight (p = 0.0005) and BMI (p = 0.001). When considered together, the 'at risk genotype'--low activity genotypes at both the MAOA and MAOB loci--shows a relative risk for obesity of 5.01. These results have not been replicated and, given the experience of complex trait genetics, warrant caution in interpretation. In implicating both the MAOA and MOAB variants, however, this study provides the first indication that dopamine availability (as opposed to other effects of MAOA) is involved in human obesity. It is therefore a priority to assess the associations in replication datasets.

Modulation of Monoamine Transporters by Common Biogenic Amines via Trace Amine-Associated Receptor 1 and Monoamine Autoreceptors in Human Embryonic Kidney 293 Cells and Brain Synaptosomes

Abstract: In brain monoaminergic systems, common biogenic amines, including dopamine, norepinephrine, and serotonin, serve as neurotransmitters. Monoamine autoreceptors provide feedback regulation in neurotransmitter release, and monoamine transporters clear the released neurotransmitters to control synaptic signaling. Recently, trace amine-associated receptor 1 (TAAR1) has been found to be expressed in brain monoaminergic nuclei and activated by common biogenic amines in vitro. This study used transfected cells and brain synaptosomes to evaluate the interaction of common biogenic amines with TAAR1 and monoamine autoreceptors and explore their modulatory effects on monoamine transporters. We confirmed that TAAR1 was activated by dopamine, norepinephrine, and serotonin and demonstrated that TAAR1 signaling was attenuated by monoamine autoreceptors at exposure to dopamine, norepinephrine, and serotonin. In transfected cells, TAAR1 in response to dopamine, norepinephrine, and serotonin significantly inhibited uptake and promoted efflux of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin, respectively, whereas the monoamine autoreceptors, D2s, α2A, and 5-HT1B enhanced the uptake function under the same condition. In brain synaptosomes, dopamine, norepinephrine, and serotonin significantly altered the uptake and efflux of [3H]dopamine, [3H]norepinephrine, and [3H]serotonin, respectively, when the monoamine autoreceptors were blocked. By comparing the effects of dopamine, norepinephrine, and serotonin in monkey and wild-type mouse synaptosomes to their effects in TAAR1 knockout mouse synaptosomes, we deduced that TAAR1 activity inhibited uptake and promoted efflux by monoamine transporters and that monoamine autoreceptors exerted opposite effects. These data provide the first evidence that common biogenic amines modulate monoamine transporter function via both TAAR1 and monoamine autoreceptors, which may balance monoaminergic activity.

Structural and Mechanistic Studies of Arylalkylhydrazine Inhibition of Human Monoamine Oxidases A and B

Abstract: The structure and mechanism of human monoamine oxidase B (MAO B) inhibition by hydrazines are investigated and compared with data on human monoamine oxidase A (MAO A). The inhibition properties of phenylethylhydrazine, benzylhydrazine, and phenylhydrazine are compared for both enzymes. Benzylhydrazine is bound more tightly to MAO B than to MAO A, and phenylhydrazine is bound weakly by either enzyme. Phenylethylhydrazine stoichiometrically reduces the covalent FAD moieties of MAO A and of MAO B. Molecular oxygen is required for the inhibition reactions, and the level of O2 consumption for phenylethylhydrazine is 6-7-fold higher with either MAO A or MAO B than for the corresponding reactions with benzylhydrazine or phenylhydrazine. Mass spectral analysis of either inhibited enzyme shows the major product is a single covalent addition of the hydrazine arylalkyl group, although lower levels of dialkylated species are detected. Absorption and mass spectral data of the inhibited enzymes show that the FAD is the major site of alkylation. The three-dimensional (2.3 A) structures of phenylethylhydrazine- and benzylhydrazine-inhibited MAO B show that alkylation occurs at the N(5) position on the re face of the covalent flavin with loss of the hydrazyl nitrogens. A mechanistic scheme is proposed to account for these data, which involves enzyme-catalyzed conversion of the hydrazine to the diazene. From literature data on the reactivities of diazenes, O2 then reacts with the bound diazene to form an alkyl radical, N2 and superoxide anion. The bound arylalkyl radical reacts with the N(5) of the flavin, while the dissociated diazene reacts nonspecifically with the enzyme through arylalkylradicals.

Determination of the oligomeric states of human and rat monoamine oxidases in the outer mitochondrial membrane and octyl beta-D-glucopyranoside micelles using pulsed dipolar electron spin resonance spectroscopy.

Abstract: Human monoamine oxidase A (hMAOA) is considered to be unique among mammalian MAOs in having a non-conservative Glu-X-Lys mutation (X being 151 in MAOAs and 142 in MAOB's), which is suggested to be the reason for its monomeric structure. This hypothesis has been tested in this work. A pargyline based nitroxide spin labeled irreversible inhibitor (ParSL) was used as a MAO active site specific spin probe to measure intersubunit distances in detergent (octyl ‚-D-glucopyranoside, OGP) purified and OMM bound forms by a pulsed dipolar ESR spectroscopic (PDS) technique. In a parallel approach, the covalent flavin cofactor present in the MAO active sites was reduced to its respective anionic flavin semiquinone and used for measuring inter-flavin distances in detergent purified samples. The measured interspin distances are within 0.1-0.3 nm of those estimated from the available dimeric crystal structures of human MAOB and rat MAOA and show that all human and rat MAOs exist as dimers in the OMM. In the OGP micelle, however, human and rat MAOAs exist only partially (e50%) as dimers, whereas human and rat MAOBs exist entirely as dimers. The Lys-151-Glu mutant of human MAOA and the Glu-142-Lys mutant of human MAOB exhibit similar spectral properties as the corresponding wild-type enzymes. Therefore, no role of the Glu-X residue in stabilizing dimeric structures of MAOs was found. The monomeric crystal structure reported for human MAOA is thus a result of its instability in the OGP micelles. The general applicability of the PDS technique to structural studies of membrane proteins in their native membrane environments and detergent purified forms is discussed.

Resistance of golden hamster to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: relationship with low levels of regional monoamine oxidase B.

Abstract: Effects of acute and chronic administration of 1 -methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were investigated for dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid, in nucleus caudatus putamen (NCP), limbic system, and substantia nigra (SN) of golden hamster and BALB/c and C57/BL mice to obtain a clue for the variance of MPTP toxicity between the strains and species. Regional differences in the levels of monoamine oxidase (MAO) and the in vitro effects of MAO inhibitors were also determined and correlated with MPTP neurotoxicity. Concentrations of MPTP in the brains of mice and golden hamster at 10 min were comparable. Golden hamster was found to be resistant to the administration of MPTP as indicated by a lack of any alteration from the normal content of DA in NCP, limbic system, and SN. Both strains of mice exhibited >50% and >75% depletion of DA (C57/BL and BALB/c, respectively). The metabolites-to-DA ratios were decreased and increased in golden hamster and mouse strains, respectively, after acute or chronic treatment. Whereas the content of total MAO in golden hamster was one-third to one-sixth of any nuclei or mitochondria of both strains of mice, the ratio of MAO A to B was significantly higher in the former species. A possible involvement of discrete regional MAO activity in determining the extent of susceptibility of a species to MPTP toxicity is indicated from the study because (1) susceptibility as evidenced by DA depletion of a species coincided with high levels of MAO activity in SN and NCP, and (2) a highly positive correlation existed with total MAO and MAO B activity, there was a lack of correlation with MAO A activity, and a negative correlation existed with MAO A-to-B ratio and DA depletion. Hence, we propose that the resistance of a species to MPTP toxicity may depend on the content as well as the ratios of the two forms of MAO in NCP and SN. In other words, a higher MAO activity and a relative dominance of MAO B in these nuclei are critical in determining the susceptibility of a species to MPTP neurotoxicity.

The increasing role of monoamine oxidase type B inhibitors in Parkinson's disease therapy.

Abstract: Background: The role of monoamine oxidase type B inhibitors in the treatment of Parkinson's disease has expanded with the new monoamine oxidase B inhibitor rasagiline and a new formulation, selegiline oral disintegrating tablets. As primary therapy in early disease monoamine oxidase B inhibitors reduce motor disability and delay the need for levodopa. In more advanced disease requiring levodopa, adjunctive monoamine oxidase B inhibitors reduce ‘off’ time and may improve gait and freezing. Objective: Rasagiline and selegiline oral disintegrating tablets may reduce the safety risks associated with the amfetamine and methamfetamine metabolites of conventional oral selegiline while retaining or improving therapeutic efficacy. Methods: Articles were identified by searches of PubMed and searches on the Internet and reviewed. All articles and other referenced materials were retrieved using the keywords ‘Parkinson's disease’, ‘treatment’ and ‘monoamine oxidase B inhibitor’ and were published between 1960 and 2007...

Gene-gene interaction between FGF20 and MAOB in Parkinson disease.

Abstract: Summary The fibroblast growth factor 20 (FGF20) and monoamine oxidase B (MAOB) genes are associated with Parkinson Disease (PD) risk and both are in the dopamine bio-pathway. Therefore, we investigated the joint effect between polymorphisms in the FGF20 and MAOB genes for evidence of interaction contributing to PD risk. Fourteen polymorphisms (eight for FGF20, six for MAOB) were genotyped in 736 families and analyzed using conditional logistic regression (CLR). Significant two-locus interactions were found in females between the polymorphisms rs1721100 of FGF20 and rs1799836 of MAOB, and between the polymorphisms rs1721082 of FGF20 and rs1799836 of MAOB. The risk alleles for each SNP identified from CLR, rs1721100 C, rs1721082 T and rs1799836 A, are consistent with previous reports. Using indicator variables for the SNP genotypes, rs1721100 GC with rs1799836 AA showed significant interaction (P = 0.021), compared with the reference group rs1721100 GG with rs1799836 GG. Using an allele-dose model for the risk alleles, rs1721100 and rs1799836 showed significant interaction (P = 0.019). We found similar interaction results between rs1721082 and rs1799836. In conclusion, variants in FGF20 and MAOB show evidence of statistical interactions, which emphasizes the importance of considering them jointly in genetic analysis of PD and illustrates potential patterns of biological interaction contributing to PD risk.

The monoamine oxidase B gene exhibits significant association to ADHD

Abstract: Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition with strong genetic basis. Recent work in China indicated that ADHD may be linked to Xp1-2 in the Han Chinese population. The gene encoding monoamine oxidase B (MAOB), the main enzyme degrading dopamine in the human brain, is located in this region. The current study sequenced the exons and the 5' and 3' flanking regions of the MAOB gene and found four common variants including 2276C>T and 2327C>T in exon 15, rs1799836 in intron 13 and rs1040399 in 3'-UTR. We assessed the association of these variants with ADHD in 548 trios collected from 468 males and 80 females probands. TDT analysis showed that alleles of each polymorphism were preferentially transmitted to probands (rs1799836, P = 3.28E-15; rs1040399, P = 1.87E-6; 2276T>C or 2327T>C, P = 2.20E-6) and haplotype-based TDT analyses also found distorted transmission. In conclusion, this study provides the strongest evidence for the involvement of MAOB gene in the etiology of ADHD to date, at least in Han Chinese population.

Therapeutic isoxazole compounds

Abstract: The invention provides a compound of formula I: wherein A1, A2, A3, R1, X, Y, and B have any of the values described herein, as well as salts of such compounds, compositions comprising such compounds, and therapeutic methods that comprise the administration of such compounds. The compounds are inhibitors of monoamine oxidase B (MAO-B) enzyme function and are useful for improving cognitive function and for treating psychiatric disorders in animals.

Comparison of the Structural Properties of the Active Site Cavities of Human and Rat Monoamine Oxidase A and B in Their Soluble and Membrane-Bound Forms†

Abstract: Structural properties of the active site cavities in human and rat monoamine oxidases (MAOA and MAOB) have been studied in their detergent-purified and outer mitochondrial membrane (OMM) bound forms using a spin-labeled irreversible inhibitor (ParSL) as an active specific spin probe. ParSL has been found to be 5−10-fold more specific for human MAOB (hMAOB) with a Ki of ca. 20 μM, compared to Ki's in the range of 100−200 μM observed for other human and rat MAOs. Solvent accessibilities of the active-site-bound spin probes have been determined by studying the power saturation properties of the spin probe EPR signals in the presence and absence of a polar paramagnetic reagent NiEDDA and by measuring the extent of spin probe reductions on treatment with excess ascorbic acid. Results presented here show that the spin probe bound to the hMAOA active site is ca. 7−8-fold more accessible than in hMAOB. In contrast, the spin probes covalently attached to the two rat enzyme active sites show comparable accessibilit...

Association of A/G Polymorphism in Intron 13 of the Monoamine Oxidase B Gene with Schizophrenia in a Spanish Population

Abstract: Background: Monoamine oxidase B (MAO-B) enzyme is involved in the oxidative metabolism of dopamine. We studied whether the A644G polymorphism in intron 13 of the MAO-B

The Neuroprotective Effect of Antidepressant Drug via Inhibition of TIEG2-MAO B Mediated Cell Death.

Abstract: Alcohol use disorders are common in the world. However, the development of novel drugs to prevent alcohol-induced brain damage is based upon an improved neurobiological understanding on the cellular changes that take place in the brain. We previously reported that ethanol exposure lowered cell proliferation and increased cell apoptosis in all cell types, but affects brain cell lines the most, while ethanol and the anti-depressant drug deprenyl, an monoamine oxidase B (MAO B) inhibitor, exposure in unison increases cell viability. Here we investigated the molecular mechanism of the neuroprotective effect of deprenyl (0.25 nM) on ethanol (75 mM)-induced harmful effect. Transforming growth factor-beta-inducible early gene 2 (TIEG2) is an activator for MAO B. MAO B levels increase has been shown to contribute to neuronal cell death. This study uses the neuronal cell line to address whether ethanol induced cell death is through the activation of TIEG2-MAO B apoptotic pathway, and whether deprenyl protects cells from the effects of alcohol through the inhibition of this pathway. We have found that ethanol exposure increases the levels of mRNA and protein/catalytic activity for both TIEG2 and MAO B, while ethanol and deprenyl exposure in unison reduce the expression of both TIEG2 and MAO B, however it increases cell viability. Additionally, TIEG2-overexpressed cells display more cellular death-induced by ethanol than control cells. In summary, this study demonstrates the role of TIEG2 in ethanol induced cell death. The inhibition of the TIEG2-MAO B pathway may be one of the mechanisms for the neuroprotective effect of deprenyl.

Both inorganic and organic selenium supplements can decrease brain monoamine oxidase B enzyme activity in adult rats.

Abstract: It has been observed that the levels of brain monoamine oxidase B (MAO-B) increase during ageing. MAO catalyses the oxidative deamination of neurotransmitters, in which the by-product H2O2 is subsequently generated. Se exists naturally in inorganic and organic forms and is considered to play a key role in antioxidation functioning. The objective of the present study was to investigate two chemical forms of Se compounds for their inhibition effect on rat brain MAO-B. The total antioxidant capacity and lipid peroxidation of rats were also examined. The rats (age 7 weeks) were divided into four groups: the control group, tocopherol group (T group, positive control), selenite group (SE group, representing the inorganic Se group) and seleno-yeast group (SY group, representing the organic Se group). The rats were fed for 11 weeks with normal diets and 12 weeks with test diets. The serum total antioxidant capacity of the SE and SY groups was significantly higher than that in the control and T groups. In rat brains and livers, the lipid peroxidation levels were significantly decreased in the T, SE and SY groups. MAO-B activity showed a significant decrease in the T, SE and SY groups in rat brains but no significant change could be noted in the rat livers. In conclusion, the present study indicates that inorganic or organic Se supplementation can decrease the brain MAO-B enzyme activity in adult rats and can be accomplished by the effect of the Se antioxidation capability.

Transtelephonic home blood pressure to assess the monoamine oxidase-B inhibitor rasagiline in Parkinson disease.

Abstract: Monoamine oxidase inhibitors are associated with dietary tyramine interactions that can induce hypertensive crises. Rasagiline mesylate is a novel irreversible selective monoamine oxidase type B inhibitor for Parkinson disease that may have a low risk of interaction with dietary tyramine because of its selectivity. To study interactions of rasagiline with diets unrestricted in tyramine-containing foods, we incorporated transtelephonic, self-monitoring of the blood pressure (BP) into a randomized, placebo-controlled trial of rasagiline 0.5 and 1.0 mg daily in 414 levodopa-treated Parkinson patients with motor fluctuations. The proportion of patients with a systolic BP increase of >30 mm Hg was the primary BP end point. In 13 968 self-measured readings at baseline, the proportion of systolic BP values that increased by >30 mm Hg after a meal ranged from 9.5% to 12.9% in the 3 treatment groups. In 25 733 BPs obtained postrandomization, the proportion of values with a >30-mm Hg systolic postprandial increase was 15% in the placebo group, 15% in the rasagiline 0.5-mg group, and 11% in the rasagiline 1-mg group after 3 weeks of double-blind therapy and 13%, 14%, and 12%, respectively, after 26 weeks of treatment (P value was not significant for all of the comparisons among treatment groups). A postprandial increase in systolic BP to >180 mm Hg at any time after randomization was seen in 3.3%, 2.6%, and 2.9% of the placebo, 0.5-mg, and 1.0-mg rasagiline groups, respectively. These data demonstrate that rasagiline did not induce postprandial hypertension in patients with Parkinson disease who were on an unrestricted diet.

Platelet monoamine oxidase activity in Down's syndrome.

Abstract: The activity of platelet monoamine oxidase in Down's syndrome cases was significantly lower than that of controls. This difference was found for both males and females, and with tyramine, tryptamine and beta-phenethylamine as substrate. The Km values of the monoamine oxidase towards tryptamine as substrate from controls and Down's syndrome patients were similar.