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https://www.readbyqxmd.com/read/27909009/association-of-protein-distribution-and-gene-expression-revealed-by-pet-and-post-mortem-quantification-in-the-serotonergic-system-of-the-human-brain
#1
A Komorowski, G M James, C Philippe, G Gryglewski, A Bauer, M Hienert, M Spies, A Kautzky, T Vanicek, A Hahn, T Traub-Weidinger, D Winkler, W Wadsak, M Mitterhauser, M Hacker, S Kasper, R Lanzenberger
Regional differences in posttranscriptional mechanisms may influence in vivo protein densities. The association of positron emission tomography (PET) imaging data from 112 healthy controls and gene expression values from the Allen Human Brain Atlas, based on post-mortem brains, was investigated for key serotonergic proteins. PET binding values and gene expression intensities were correlated for the main inhibitory (5-HT1A) and excitatory (5-HT2A) serotonin receptor, the serotonin transporter (SERT) as well as monoamine oxidase-A (MAO-A), using Spearman's correlation coefficients (rs) in a voxel-wise and region-wise analysis...
November 30, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27900600/antidepressant-like-effect-of-isorhynchophylline-in-mice
#2
Yan-Fang Xian, Ding Fan, Siu-Po Ip, Qing-Qiu Mao, Zhi-Xiu Lin
Isorhynchophylline (IRN), an oxindole alkaloid, has been identified as the main active ingredient responsible for the biological activities of Uncaria rhynchophylla (Miq) Miq ex Havil. (Rubiaceae). Previous studies in our laboratory have revealed that IRN possesses potent neuroprotective effects in different models of Alzheimer's disease. However, the antidepressant-like effects of IRN are remained unclear. The present study aims to evaluate the antidepressant-like effects of IRN. The antidepressant-like effects of IRN was determined by using animal models of depression including forced swimming and tail suspension tests...
November 30, 2016: Neurochemical Research
https://www.readbyqxmd.com/read/27896136/attention-deficit-hyperactivity-disorder-suffers-from-mitochondrial-dysfunction
#3
Poonam Verma, Alpana Singh, Dominic Ngima Nthenge-Ngumbau, Usha Rajamma, Swagata Sinha, Kanchan Mukhopadhyay, Kochupurackal P Mohanakumar
BACKGROUND: Pathophysiology of attention-deficit hyperactivity disorder (ADHD) is not known, and therefore the present study investigated mitochondrial defects, if any in cybrids created from patients and control population. METHODS: To investigate mitochondrial pathology in ADHD, cybrids cell lines were created from ADHD probands and controls by fusing their platelets with ρ(0)-cells prepared from SH-SY5Y neuroblastoma cell line. Cellular respiration, oxidative stress, mitochondrial membrane potential and morphology were evaluated employing oxygraph, mitochondria-specific fluorescence staining and evaluation by FACS, and immunocytochemistry...
December 2016: BBA Clinical
https://www.readbyqxmd.com/read/27884068/silver-nanoparticle-exposure-in-pregnant-rats-increases-gene-expression-of-tyrosine-hydroxylase-and-monoamine-oxidase-in-offspring-brain
#4
Seyed Reza Fatemi Tabatabaie, Babak Mehdiabadi, Najmeh Mori Bakhtiari, Mohammad Reza Tabandeh
CONTEXT: Maternal exposure to silver nanoparticles (AgNPs) affects neurobehavioral reflexes and spatial memory formation in offspring. Although the transmission of AgNPs into the brain has been reported, its toxic effect on dopamine metabolism in the brain of offspring has not been studied so far. OBJECTIVE: The aim of the present study was to investigate the expression levels of tyrosine hydroxylase (TH) and monoamine oxidase A (MAO-A) genes in the brain of offspring exposed in utero to various concentrations of AgNPs...
November 24, 2016: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/27866207/post-stroke-fatigue-may-be-associated-with-the-promoter-region-of-a-monoamine-oxidase-a-gene-polymorphism
#5
Smi Choi-Kwon, Mihye Ko, Sang-Eun Jun, Juhan Kim, Kyung-Hee Cho, Hyun-Wook Nah, Hasup Song, Jong S Kim
BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A)...
November 19, 2016: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27863747/symmetrical-aryl-linked-bis-iminothiazolidinones-as-new-chemical-entities-for-the-inhibition-of-monoamine-oxidases-synthesis-in-vitro-biological-evaluation-and-molecular-modelling-analysis
#6
Naeem Abbas, Sumera Zaib, Syeda Mahwish Bakht, Aliya Ibrar, Imtiaz Khan, Sadaf Batool, Aamer Saeed, Jamshed Iqbal
The multifactorial nature of Parkinson's disease necessitates the development of new chemical entities with inherent ability to address key pathogenic processes. To this end, two series of new symmetrical 1,2- and 1,4-bis(2-aroyl/alkoylimino-5-(2-methoxy-2-oxoethylidene)-4-oxo-thiazolidin-3-yl)benzene derivatives (3a-g and 5a-e) were synthesized in good yields by the cyclization of 1,2- and 1,4-bis(N'-substituted thioureido)benzene intermediates with dimethyl acetylenedicarboxylate (DMAD) in methanol at ambient temperature...
November 9, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27861613/non-serotonergic-neurotoxicity-by-mdma-ecstasy-in-neurons-derived-from-mouse-p19-embryonal-carcinoma-cells
#7
Dina Popova, Andréas Forsblad, Sanaz Hashemian, Stig O P Jacobsson
3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is a commonly abused recreational drug that causes neurotoxic effects in both humans and animals. The mechanism behind MDMA-induced neurotoxicity is suggested to be species-dependent and needs to be further investigated on the cellular level. In this study, the effects of MDMA in neuronally differentiated P19 mouse embryonal carcinoma cells have been examined. MDMA produces a concentration-, time- and temperature-dependent toxicity in differentiated P19 neurons, as measured by intracellular MTT reduction and extracellular LDH activity assays...
2016: PloS One
https://www.readbyqxmd.com/read/27806193/neuroprotective-effect-of-a-new-7-8-dihydroxycoumarin-based-fe2-cu2-chelator-in-cell-and-animal-models-of-parkinson-s-disease
#8
Pabla Aguirre, Olimpo García-Beltrán, Victoria Tapia, Yorka Muñoz, Bruce Kennedy Cassels, Marco T Nunez
Disturbed iron homeostasis, often coupled to mitochondrial dysfunction, plays an important role in the progression of common neurodegenerative diseases such as Parkinson disease (PD). Recent studies have underlined the relevance of iron chelation therapy for the treatment of these diseases. Here we describe the synthesis, chemical and biological characterization of the multifunctional chelator 7,8-dihydroxy-4-((methylamino)methyl)-2H-chromen-2-one (DHC12). Metal selectivity of DHC12 was Cu2+ ̴ Fe2+ > Zn2+ > Fe3+...
November 2, 2016: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/27803666/inhibitors-of-mao-a-and-mao-b-in-psychiatry-and-neurology
#9
REVIEW
John P M Finberg, Jose M Rabey
Inhibitors of MAO-A and MAO-B are in clinical use for the treatment of psychiatric and neurological disorders respectively. Elucidation of the molecular structure of the active sites of the enzymes has enabled a precise determination of the way in which substrates and inhibitor molecules are metabolized, or inhibit metabolism of substrates, respectively. Despite the knowledge of the strong antidepressant efficacy of irreversible MAO inhibitors, their clinical use has been limited by their side effect of potentiation of the cardiovascular effects of dietary amines ("cheese effect")...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27754693/isolation-of-acacetin-from-calea-urticifolia-with-inhibitory-properties-against-human-monoamine-oxidase-a-and-b
#10
Narayan D Chaurasiya, Vedanjali Gogineni, Khaled M Elokely, Francisco León, Marvin J Núñez, Michael L Klein, Larry A Walker, Stephen J Cutler, Babu L Tekwani
Calea urticifolia (Asteraceae: Asteroideae) has long been used as a traditional medicine in El Salvador to treat arthritis and fever, among other illnesses. The chloroform extract of the leaves of C. urticifolia showed potent inhibition of recombinant human monoamine oxidases (MAO-A and -B). Further bioassay-guided fractionation led to the isolation of a flavonoid, acacetin, as the most prominent MAO inhibitory constituent, with IC50 values of 121 and 49 nM for MAO-A and -B, respectively. The potency of MAO inhibition by acacetin was >5-fold higher for MAO-A (0...
October 18, 2016: Journal of Natural Products
https://www.readbyqxmd.com/read/27747875/identification-of-compounds-from-non-polar-fractions-of-blechnum-spp-and-a-multitarget-approach-involving-enzymatic-modulation-and-oxidative-stress
#11
Juliana Maria de Mello Andrade, Natasha Maurmann, Patricia Pranke, Izabel Cristina Casanova Turatti, Norberto Peporine Lopes, Amélia T Henriques
OBJECTIVES: The hexane (HEX) and dichloromethane (DCM) fractions from Blechnum binervatum, Blechnum brasiliense and Blechnum occidentale were studied about phytochemicals and biological properties using multitarget approach. METHODS: The chemical composition was performed by gas chromatography coupled with mass spectrometry detector (GC-MS) analysis. Antioxidant capacity was evaluated against free radicals and on lipid peroxidation. Monoamine oxidases (MAO) and cholinesterases enzymatic modulation, as well as effects on rat and human cells, were assessed...
October 17, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/27734680/empirical-valence-bond-simulations-of-the-hydride-transfer-step-in-the-monoamine-oxidase-a-catalyzed-metabolism-of-noradrenaline
#12
Matic Poberznik, Miha Purg, Matej Repič, Janez Mavri, Robert Vianello
Monoamine oxidases (MAOs) A and B are flavoenzymes responsible for the metabolism of biogenic amines such as dopamine, serotonin and noradrenaline, which is why they have been extensively implicated in the etiology and course of various neurodegenerative disorders, and, accordingly, used as primary pharmacological targets to treat these debilitating cognitive diseases. The precise chemical mechanism through which MAOs regulate the amine concentration, which is vital for the development of novel inhibitors, is still not unambiguously determined in the literature...
October 13, 2016: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/27725503/2-azolylchromone-derivatives-as-potent-and-selective-inhibitors-of-monoamine-oxidases-a-and-b
#13
Koichi Takao, Takayuki Saito, Daisuke Chikuda, Yoshiaki Sugita
A series of 2-azolylchromone derivatives were synthesized and their monoamine oxidase (MAO) A and B inhibitory activities were evaluated. Of the synthesized compounds, compounds 1b, 2b, 4a-c, 5b and 7b showed potent inhibitory activities against MAO-A (IC50 values, 1b: 0.32 µM; 2b: 0.14 µM; 4a: 0.11 µM; 4b: 0.023 µM; 4c: 0.15 µM; 5b: 0.59 µM; 7b: 0.19 µM) and 4a, c, 5a, c, 6c and 8c for MAO-B (IC50 values, 4a: 0.028 µM; 4c: 0.019 µM; 5a: 0.73 µM; 5c: 0.28 µM; 6c: 0.28 µM; 8c: 0...
2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27715253/an-overview-of-analytical-methods-for-the-determinationof-monoamine-oxidase-inhibitors-in-pharmaceutical-formulations-and-biological-fluids
#14
Cafer Saka
Monoamine oxidase inhibitors (MAOIs) were the first type of antidepressant developed. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. They are also used in the treatment of Parkinson's disease, tuberculosis, and several other disorders. Therefore, it is very important to develop efficient analytical methods for monitoring and management. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. In this article, analyses of MAOIs in pharmaceutical formulations and biological fluids were reviewed from 2000 to the present, including all types of chromatographic, spectrophotometric, electrophoretic, and voltammetric techniques, focusing on isoniazid, tranylcypromine, moclobemide, rasagiline, and selegiline...
October 7, 2016: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/27692996/neuroprotective-effects-of-benzyloxy-substituted-small-molecule-monoamine-oxidase-b-inhibitors-in-parkinson-s-disease
#15
Zhimin Wang, Jiajia Wu, Xuelian Yang, Pei Cai, Qiaohong Liu, Kelvin D G Wang, Lingyi Kong, Xiaobing Wang
The benzyloxy substituted small molecules are well-known highly potent monoamine oxidase B inhibitors, but their therapeutic potential against Parkinson's disease have not been investigated in detail. In this paper, a series of representative benzyloxy substituted derivatives were synthesized and evaluated for MAO-A/B inhibition. In addition, their neuroprotective effects were investigated in 6-OHDA- and rotenone-treated PC12 cells. It was observed that most of the compounds exhibited a marked increase in survival of PC12 cells which treated with the neurotoxins...
September 21, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27686269/phytochemical-and-ethnomedicinal-study-of-huperzia-species-used-in-the-traditional-medicine-of-saraguros-in-southern-ecuador-ache-and-mao-inhibitory-activity
#16
Chabaco Armijos, Gianluca Gilardoni, Luis Amay, Antonio Lozano, Francesco Bracco, Jorge Ramirez, Nicole Bec, Christian Larroque, Paola Vita Finzi, Giovanni Vidari
ETHNOBOTANICAL AND ETHNOMEDICINAL RELEVANCE: This study concerns seven Huperzia species (Lycopodiaceae), namely H. brevifolia, H. columnaris, H. compacta, H. crassa, H. espinosana, H. tetragona, H. weberbaueri, which are considered sacred plants by the Saraguro community, living in the Southern Andes of Ecuador; these plants are widely used in traditional medicine and ritual ceremonies. MATERIAL AND METHODS: The plants were selected on the basis of written interviews with 10 visionary healers (yachak) (2 women, 8 men), indicated as the most credible by the Saraguro Healers Council...
September 26, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27666135/rapid-synthesis-of-flavone-based-monoamine-oxidase-mao-inhibitors-targeting-two-active-sites-using-click-chemistry
#17
Wei Zhen Jia, Feng Cheng, Yin Jun Zhang, Jin Yan Ge, Shao Q Yao, Qing Zhu
A new library of flavone derivatives targeting two active sites of monoamine oxidases ("aromatic cage" and substrate cavity) were designed and synthesized using click chemistry (CuAAC reaction) between 6-N3 -2-phenyl chromones (Az1-Az2) and a series of alkynes (k1-k20). Their inhibitory activities against MAO isoforms (MAO-A and MAO-B) are evaluated. Compounds with fluorine, amide bonds, or amino bonds have shown better inhibition. The most potent flavone MAO inhibitor studied is Az2k19 (1.6 μm for MAO-A, 2...
September 26, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27662218/2-heteroarylidene-1-indanone-derivatives-as-inhibitors-of-monoamine-oxidase
#18
Magdalena S Nel, Anél Petzer, Jacobus P Petzer, Lesetja J Legoabe
In the present study a series of fifteen 2-heteroarylidene-1-indanone derivatives were synthesised and evaluated as inhibitors of recombinant human monoamine oxidase (MAO) A and B. These compounds are structurally related to series of heterocyclic chalcone derivatives which have previously been shown to act as MAO-B specific inhibitors. The results document that the 2-heteroarylidene-1-indanones are in vitro inhibitors of MAO-B, displaying IC50 values of 0.0044-1.53μM. Although with lower potencies, the derivatives also inhibit the MAO-A isoform with IC50 values as low as 0...
September 17, 2016: Bioorganic Chemistry
https://www.readbyqxmd.com/read/27660276/in-vitro-effects-of-cognitives-and-nootropics-on-mitochondrial-respiration-and-monoamine-oxidase-activity
#19
Namrata Singh, Jana Hroudová, Zdeněk Fišar
Impairment of mitochondrial metabolism, particularly the electron transport chain (ETC), as well as increased oxidative stress might play a significant role in pathogenesis of Alzheimer's disease (AD). Some effects of drugs used for symptomatic AD treatment may be related to their direct action on mitochondrial function. In vitro effects of pharmacologically different cognitives (galantamine, donepezil, rivastigmine, 7-MEOTA, memantine) and nootropic drugs (latrepirdine, piracetam) were investigated on selected mitochondrial parameters: activities of ETC complexes I, II + III, and IV, citrate synthase, monoamine oxidase (MAO), oxygen consumption rate, and hydrogen peroxide production of pig brain mitochondria...
September 23, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27634040/activity-dependent-regulation-of-histone-lysine-demethylase-kdm1a-by-a-putative-thiol-disulfide-switch
#20
Emily L Ricq, Jacob M Hooker, Stephen J Haggarty
Lysine demethylation of proteins such as histones is catalyzed by several classes of enzymes, including the FAD-dependent amine oxidases KDM1A/B. The KDM1 family is homologous to the mitochondrial monoamine oxidases MAO-A/B and produces hydrogen peroxide in the nucleus as a byproduct of demethylation. Here, we show KDM1A is highly thiol-reactive in vitro and in cellular models. Enzyme activity is potently and reversibly inhibited by the drug disulfiram and by hydrogen peroxide. Hydrogen peroxide produced by KDM1A catalysis reduces thiol labeling and inactivates demethylase activity over time...
November 18, 2016: Journal of Biological Chemistry
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