神経細胞内のミトコンドリア外膜に局在 (SPC.67)
カテコラミンを酸化的脱アミノ化する (SPC.67)
２つのisoformが存在するが、MAO_Bは、ドパミン、チラミンを特異的な基質とする (SPC.67)

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Massachusetts / mental age

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/02/23 16:21:40」(JST)

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Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene.

The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important^{[citation needed]} role in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine.^[1] Like MAOA, it also degrades dopamine.

Structure

Monoamine oxidase B has a hydrophobic bipartite elongated cavity that (for the "open" conformation) occupies a combined volume close to 700 Å³. hMAO-A has a single cavity that exhibits a rounder shape and is larger in volume than the "substrate cavity" of hMAO-B.^[2]

The first cavity of hMAO-B has been termed the entrance cavity (290 Å³), the second substrate cavity or active site cavity (~390 Å³) – between both an isoleucine199 side-chain serves as a gate. Depending on the substrate or bound inhibitor, it can exist in either an open or a closed form, which has been shown to be important in defining the inhibitor specificity of hMAO B. At the end of the substrate cavity is the FAD coenzyme with sites for favorable amine binding about the flavin involving two nearly parallel tyrosyl (398 and 435) residues that form what has been termed an aromatic cage.^[2]

Differences between MAOA and MAOB

MAO-A is involved in the metabolism of tyramine; inhibition, in particular irreversible inhibition of MAO-A can result in a dangerous pressor effect when foods high in tyramine are consumed such as cheeses. MAO-A is involved in the metabolism of serotonin, noradrenaline and dopamine where as MAO-B metabolises the dopamine neurotransmitter.^[3] MAO-B is an enzyme on the outer mitochondrial membrane and catalyzes the oxidation of arylalkylamine neurotransmitters^[4]

Monoamine oxidase A (MAOA) generally metabolizes tyramine, norepinephrine (NE), serotonin (5-HT), and dopamine (DA) (and other less clinically relevant chemicals). In contrast, Monoamine oxidase B (MAOB) mainly metabolizes dopamine (DA) (and other less clinically relevant chemicals). The differences between the substrate selectivity of the two enzymes are utilized clinically when treating specific disorders: Monoamine oxidase A inhibitors have been typically used in the treatment of depression, and monoamine oxidase B inhibitors are typically used in the treatment of Parkinson's disease.^[5]^[6] Nonspecific (i.e. MAOA/B combined) inhibitors can pose problems when taken concomitantly with tyramine-containing foods such as cheese, because the drug's inhibition of MAOA causes a dangerous elevation of serum tyramine levels, which can lead to hypertensive symptoms. Selective MAOB inhibitors bypass this problem by preferentially inhibiting MAOB, which mostly metabolizes DA. If MAOB is inhibited, then more DA is available for proper neuronal function, especially in Parkinson's Disease.

Roles in disease and aging

Alzheimer's disease and Parkinson's disease are both associated with elevated levels of MAO-B in the brain.^[7]^[8] The normal activity of MAO-B creates reactive oxygen species, which directly damage cells.^[9] MAO-B levels have been found to increase with age, suggesting a role in natural age related cognitive decline and the increased likelihood of developing neurological diseases later in life.^[10] More active polymorphisms of the MAOB gene have been linked to negative emotionality, and suspected as an underlying factor in depression.^[11] Activity of MAO-B has also been shown to play a role in stress-induced cardiac damage.^[12]^[13]

Animal models

Transgenic mice that are unable to produce MAO-B are shown to be resistant to a mouse model of Parkinson's disease.^[14]^[15]^[16] They also demonstrate increased responsiveness to stress (as with MAO-A knockout mice)^[17] and increased β-PEA.^[15]^[17] In addition, they exhibit behavioral disinhibition and reduced anxiety-like behaviors.^[18]

Inhibition of MAO-B in rats has been shown to prevent many age-related biological changes such as optic nerve degeneration, and extend average lifespan by up to 39%.^[19]^[20]

Effects of deficiency in humans

While people lacking the gene for MAO-A display mental retardation and behavioral abnormalities, people lacking the gene for MAO-B display no abnormalities except elevated phenethylamine levels in urine, raising the question of whether MAO-B is actually a necessary enzyme. Newer research indicates the importance of phenethylamine and other trace amines, which are now known to regulate catecholamine and serotonin neurotransmission through the same receptor as amphetamine, TAAR1.^[21]^[22]

The prophylactic use of MAO-B inhibitors to slow natural human aging in otherwise healthy individuals has been proposed, but remains a highly controversial topic.^[23]^[24]

Selective inhibitors

Geiparvarin

(+)-Catechin

Structural formulae of high-affinity reversible MAO inhibitors selective for type B

Species-dependent divergences may hamper the extrapolation of inhibitor potencies.^[25]

Reversible

Natural

Geiparvarin^[26]
Desmethoxyyangonin,^[27] a constituent of kava extract; modest affinity
Catechin and epicatechin

Synthetic

Safinamide and analogs^[28]
5H-Indeno[1,2-c]pyridazin-5-ones^[25]^[29]^[30] (see 3d model)
Substituted chalcones^[31]
2-(N-Methyl-N-benzylaminomethyl)-1H-pyrrole^[32]
1-(4-Arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazine^[33]
2-Thiazolylhydrazone^[34]
3,5-Diaryl pyrazole^[35]
Pyrazoline derivatives^[36]^[37]
Several coumarin derivatives^[38] and #C19*^[25] (see 3d model)
Phenylcoumarins, extremely subtype selective^[39] and further analogs^[40]^[41]^[42] (see 3d model)
Chromone-3-phenylcarboxamides^[43]
Isatins^[44]
Phthalimides^[45]
8-Benzyloxycaffeines^[46]^[47] and CSC analogs^[48]
(E,E)-8-(4-phenylbutadien-1-yl)caffeines,^[49] with A_2A antagonistic component
Indazole- and Indole-5-carboxamides^[50]

Irreversible (covalent)

Selegiline (Eldepryl, Zelapar, Emsam)
Rasagiline (Azilect)

References

^ "Entrez Gene: MAOB monoamine oxidase B".
^ ^a ^b Edmondson D, Binda C, Mattevi A (August 2007). "Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B". Arch. Biochem. Biophys. 464 (2): 269–76. doi:10.1016/j.abb.2007.05.006. PMC 1993809. PMID 17573034.
^ Youdim M, Weinstock M (January 2004). "Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation". Neurotoxicology 25 (1–2): 243–50. doi:10.1016/S0161-813X(03)00103-7. PMID 14697899.
^ Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson D et al. (March 2004). "Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class". J. Med. Chem. 47 (7): 1767–74. doi:10.1021/jm031087c. PMID 15027868.
^ Nolen W, Hoencamp E, Bouvy P, Haffmans P (1993). "Reversible monoamine oxidase-A inhibitors in resistant major depression". Clin Neuropharmacol 16 (Suppl 2): S69–76. PMID 8313400.
^ Riederer P, Laux G (March 2011). "MAO-inhibitors in Parkinson's Disease". Exp Neurobiol 20 (1): 1–17. doi:10.5607/en.2011.20.1.1. PMC 3213739. PMID 22110357.
^ Saura J, Luque J, Cesura A, Da Prada M, Chan-Palay V, Huber G et al. (September 1994). "Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography". Neuroscience 62 (1): 15–30. doi:10.1016/0306-4522(94)90311-5. PMID 7816197.
^ Mallajosyula J, Chinta S, Rajagopalan S, Nicholls D, Andersen J (October 2009). "Metabolic control analysis in a cellular model of elevated MAO-B: relevance to Parkinson's disease". Neurotox Res 16 (3): 186–93. doi:10.1007/s12640-009-9032-2. PMC 2727365. PMID 19526285.
^ Nagatsu T, Sawada M (2006). "Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson's disease: possible implications of glial cells". J. Neural Transm. Suppl. Journal of Neural Transmission. Supplementa 71 (71): 53–65. doi:10.1007/978-3-211-33328-0_7. ISBN 978-3-211-33327-3. PMID 17447416.
^ Kumar M, Andersen J (August 2004). "Perspectives on MAO-B in aging and neurological disease: where do we go from here?". Mol. Neurobiol. 30 (1): 77–89. doi:10.1385/MN:30:1:077. PMID 15247489.
^ Dlugos A, Palmer A, de Wit H (October 2009). "Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans". J Neural Transm 116 (10): 1323–34. doi:10.1007/s00702-009-0281-2. PMC 3653168. PMID 19657584.
^ Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N (July 2011). "Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury". Biochim. Biophys. Acta 1813 (7): 1323–32. doi:10.1016/j.bbamcr.2010.09.010. PMC 3030628. PMID 20869994.
^ Kaludercic N, Carpi A, Nagayama T, Sivakumaran V, Zhu G, Lai E et al. (January 2014). "Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts". Antioxid. Redox Signal. 20 (2): 267–80. doi:10.1089/ars.2012.4616. PMC 3887464. PMID 23581564.
^ Shih J, Chen K (1999). "MAO-A and -B gene knock-out mice exhibit distinctly different behavior". Neurobiology (Bp) 7 (2): 235–46. PMID 10591056.
^ ^a ^b Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams J et al. (October 1997). "Increased stress response and beta-phenylethylamine in MAOB-deficient mice.". Nature Genetics 17 (2): 206–10. doi:10.1038/ng1097-206. PMID 9326944.
^ Shih J, Chen K, Ridd M (1999). "Monoamine oxidase: from genes to behavior.". Annual review of neuroscience 22: 197–217. doi:10.1146/annurev.neuro.22.1.197. PMC 2844879. PMID 10202537.
^ ^a ^b Shih J (January 2004). "Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B.". Neurotoxicology 25 (1–2): 21–30. doi:10.1016/s0161-813x(03)00112-8. PMID 14697877.
^ Bortolato M, Godar S, Davarian S, Chen K, Shih J (December 2009). "Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice.". Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 34 (13): 2746–57. doi:10.1038/npp.2009.118. PMC 2783894. PMID 19710633.
^ Nebbioso M, Pascarella A, Cavallotti C, Pescosolido N (December 2012). "Monoamine oxidase enzymes and oxidative stress in the rat optic nerve: age-related changes". Int J Exp Pathol 93 (6): 401–5. doi:10.1111/j.1365-2613.2012.00832.x. PMC 3521895. PMID 23082958.
^ Kitani K, Kanai S, Sato Y, Ohta M, Ivy G, Carrillo M (1993). "Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence". Life Sci. 52 (3): 281–8. doi:10.1016/0024-3205(93)90219-S. PMID 8423709.
^ Lenders J, Eisenhofer G, Abeling N, Berger W, Murphy D, Konings C et al. (February 1996). "Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes". J. Clin. Invest. 97 (4): 1010–9. doi:10.1172/JCI118492. PMC 507147. PMID 8613523.
^ Miller G (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.
^ Miklya I (December 2009). "[Slowing the age-induced decline of brain function with prophylactic use of (−)-deprenyl (Selegiline, Jumex). Current international view and conclusions 25 years after the Knoll's proposal]". Neuropsychopharmacol Hung (in Hungarian) 11 (4): 217–25. PMID 20150659.
^ Ukraintseva S, Arbeev K, Michalsky A, Yashin A (June 2004). "Antiaging treatments have been legally prescribed for approximately thirty years". Ann. N. Y. Acad. Sci. 1019: 64–9. doi:10.1196/annals.1297.014. PMID 15246996.
^ ^a ^b ^c Novaroli L, Daina A, Favre E, Bravo J, Carotti A, Leonetti F et al. (October 2006). "Impact of species-dependent differences on screening, design, and development of MAO B inhibitors". J. Med. Chem. 49 (21): 6264–72. doi:10.1021/jm060441e. PMID 17034132.
^ Carotti A, Carrieri A, Chimichi S, Boccalini M, Cosimelli B, Gnerre C et al. (December 2002). "Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies". Bioorg. Med. Chem. Lett. 12 (24): 3551–5. doi:10.1016/S0960-894X(02)00798-9. PMID 12443774.
^ Uebelhack R, Franke L, Schewe H (September 1998). "Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)". Pharmacopsychiatry 31 (5): 187–92. doi:10.1055/s-2007-979325. PMID 9832350.
^ Leonetti F, Capaldi C, Pisani L, Nicolotti O, Muncipinto G, Stefanachi A et al. (October 2007). "Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase". Journal of Medicinal Chemistry 50 (20): 4909–16. doi:10.1021/jm070725e. PMID 17824599.
^ compound #2d, Frédérick R, Dumont W, Ooms F, Aschenbach L, Van der Schyf C, Castagnoli N et al. (June 2006). "Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core". J. Med. Chem. 49 (12): 3743–7. doi:10.1021/jm051091j. PMID 16759116.
^ Carotti A, Catto M, Leonetti F, Campagna F, Soto-Otero R, Méndez-Alvarez E et al. (November 2007). "Synthesis and monoamine oxidase inhibitory activity of new pyridazine-, pyrimidine- and 1,2,4-triazine-containing tricyclic derivatives". Journal of Medicinal Chemistry 50 (22): 5364–71. doi:10.1021/jm070728r. PMID 17910428.
^ Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F et al. (May 2009). "Chalcones: a valid scaffold for monoamine oxidases inhibitors". J. Med. Chem. 52 (9): 2818–24. doi:10.1021/jm801590u. PMID 19378991.
^ compound #21, Silvestri R, La Regina G, De Martino G, Artico M, Befani O, Palumbo M et al. (March 2003). "Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B". J. Med. Chem. 46 (6): 917–20. doi:10.1021/jm0256124. PMID 12620068.
^ compound # (R)-8b, Chimenti F, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S et al. (September 2010). "Synthesis, stereochemical separation, and biological evaluation of selective inhibitors of human MAO-B: 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines". J. Med. Chem. 53 (17): 6516–20. doi:10.1021/jm100120s. PMID 20715818.
^ compound #18, Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A et al. (February 2007). "Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives". J. Med. Chem. 50 (4): 707–12. doi:10.1021/jm060869d. PMID 17253676.
^ compound #3g, Chimenti F, Fioravanti R, Bolasco A, Manna F, Chimenti P, Secci D et al. (February 2007). "Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors". J. Med. Chem. 50 (3): 425–8. doi:10.1021/jm060868l. PMID 17266193.
^ compound #(S)-1, Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A et al. (November 2005). "Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives". J. Med. Chem. 48 (23): 7113–22. doi:10.1021/jm040903t. PMID 16279769.
^ Mishra N, Sasmal D (April 2011). "Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation". Bioorg. Med. Chem. Lett. 21 (7): 1969–73. doi:10.1016/j.bmcl.2011.02.030. PMID 21377879.
^ compound #41, Catto M, Nicolotti O, Leonetti F, Carotti A, Favia A, Soto-Otero R et al. (2006). "Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches". Journal of Medicinal Chemistry 49 (16): 4912–25. doi:10.1021/jm060183l. PMID 16884303.
^ compound #2, Matos M, Vazquez-Rodriguez S, Uriarte E, Santana L, Viña D (July 2011). "MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins". Bioorg. Med. Chem. Lett. 21 (14): 4224–7. doi:10.1016/j.bmcl.2011.05.074. PMID 21684743.
^ Matos M, Viña D, Janeiro P, Borges F, Santana L, Uriarte E (September 2010). "New halogenated 3-phenylcoumarins as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 20 (17): 5157–60. doi:10.1016/j.bmcl.2010.07.013. PMID 20659799.
^ Matos M, Viña D, Picciau C, Orallo F, Santana L, Uriarte E (September 2009). "Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 19 (17): 5053–5. doi:10.1016/j.bmcl.2009.07.039. PMID 19628387.
^ Matos M, Viña D, Quezada E, Picciau C, Delogu G, Orallo F et al. (June 2009). "A new series of 3-phenylcoumarins as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 19 (12): 3268–70. doi:10.1016/j.bmcl.2009.04.085. PMID 19423346.
^ compound #9, #12, Gaspar A, Reis J, Fonseca A, Milhazes N, Viña D, Uriarte E et al. (January 2011). "Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 21 (2): 707–9. doi:10.1016/j.bmcl.2010.11.128. PMID 21194943.
^ compound #9i, Manley-King C, Bergh J, Petzer J (January 2011). "Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues". Bioorg. Med. Chem. 19 (1): 261–74. doi:10.1016/j.bmc.2010.11.028. PMID 21134756.
^ compound #5c, Manley-King C, Bergh J, Petzer J (August 2011). "Inhibition of monoamine oxidase by C5-substituted phthalimide analogues". Bioorg. Med. Chem. 19 (16): 4829–40. doi:10.1016/j.bmc.2011.06.070. PMID 21778064.
^ Strydom B, Bergh J, Petzer J (August 2011). "8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase". Eur J Med Chem 46 (8): 3474–85. doi:10.1016/j.ejmech.2011.05.014. PMID 21621312.
^ Strydom B, Malan S, Castagnoli N, Bergh J, Petzer J (February 2010). "Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues". Bioorg. Med. Chem. 18 (3): 1018–28. doi:10.1016/j.bmc.2009.12.064. PMID 20093036.
^ Vlok N, Malan S, Castagnoli N, Bergh J, Petzer J (May 2006). "Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC)". Bioorg. Med. Chem. 14 (10): 3512–21. doi:10.1016/j.bmc.2006.01.011. PMID 16442801.
^ Pretorius J, Malan S, Castagnoli N, Bergh J, Petzer J (September 2008). "Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues". Bioorganic & Medicinal Chemistry 16 (18): 8676–84. doi:10.1016/j.bmc.2008.07.088. PMID 18723354.
^ Tzvetkov et al. (2014): "Indazole- and Indole-5-carboxamides: Selective and Reversible Monoamine Oxidase B Inhibitors with Subnanomolar Potency". Journal of Medicinal Chemistry. epub.

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1. 成人におけるうつ病治療としてのモノアミン酸化酵素阻害剤（MAOI）monoamine oxidase inhibitors maois for treating depressed adults [show details]
…largely responsible for the MAOIs antidepressant effects. The enzyme MAO comes in two forms, MAOa and MAOb. MAOb metabolizes phenylethylamine and, together with MAOa, breaks down dopamine. MAOa is responsible …
2. 肝性脳症：病因hepatic encephalopathy pathogenesis [show details]
…with alterations in the number of 5HT1A and 5HT2 receptors and increased activity of both MAOA and MAOB (enzymes catabolizing 5-HT) . These findings suggest an increased serotonin turnover rate in HE, but…

English Journal

Pathways involved in sasang constitution from genome-wide analysis in a korean population.

Kim BY, Yu SG, Kim JY, Song KH.SourceDivision of Constitutional Medicine Research, Korea Institute of Oriental Medicine , Daejeon, Republic of Korea.
Journal of alternative and complementary medicine (New York, N.Y.).J Altern Complement Med.2012 Nov;18(11):1070-80. doi: 10.1089/acm.2011.0434. Epub 2012 Aug 13.
Abstract Objective: Sasang constitution (SC) medicine, a branch of Korean traditional medicine, classifies the individual into one of four constitutional types (Taeum, TE; Soeum, SE; Soyang, SY; and Taeyang, TY) based on physiologic characteristics. The authors of the current article recently repo
PMID 22889377

MAOA and MAOB polymorphisms and anger-related traits in suicidal participants and controls.

Antypa N, Giegling I, Calati R, Schneider B, Hartmann AM, Friedl M, Konte B, Lia L, De Ronchi D, Serretti A, Rujescu D.SourceDepartment of Biomedical and NeuroMotor Sciences, University of Bologna, Viale Carlo Pepoli 5, 40123, Bologna, Italy.
European archives of psychiatry and clinical neuroscience.Eur Arch Psychiatry Clin Neurosci.2012 Oct 31. [Epub ahead of print]
MAOA and, to a lesser extent, MAOB polymorphisms have been related to aggression traits and suicidality. We aimed to investigate the role of MAOA and MAOB in suicidal versus non-suicidal participants and interactions between genetic variation and suicidal status on aggression and anger-related trait
PMID 23111930

Japanese Journal

MAOB阻害薬 (特集日常よく遭遇するパーキンソン病--パーキンソン病はここまでわかった)

山田人志
成人病と生活習慣病 38(8), 959-962, 2008-08
NAID 40016230269

犬のモノアミン酸化酵素B遺伝子におけるシステインへからアルギニンのアミノ酸置換を伴う一塩基多型の同定(短報)(動物行動学)

橋爪千恵,増田宏司,桃沢幸秀,菊水健史,武内ゆかり,森裕司
The journal of veterinary medical science 67(2), 199-201, s・iii, 2005-02-25
… モノアミン酸化酵素B(MAOB)遺伝子の塩基配列において,システインからアルギニンへのアミノ酸置換を伴う一塩基多型を同定した.ゴールデンレトリーバー,ラブラドールレトリーバー,マルチーズ,ミニチュアシュナウザーおよびシバの5犬種間で遺伝子多型出現頻度を比較したところ犬種間に有意な差が認められ,脳内神経伝達に関する酵素の遺伝子多型が行動様式の犬種差に関連する可能性が示唆された. …
NAID 110003963703

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拡張検索	「MAOB inhibitors」
関連記事	「MA」「MAO」

「MAOB inhibitors」

Monoamine oxidase B
	; PDB rendering based on 1gos.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1GOS, 1H8R, 1OJ9, 1OJA, 1OJC, 1OJD, 1S2Q, 1S2Y, 1S3B, 1S3E, 2BK3, 2BK4, 2BK5, 2BYB, 2C64, 2C65, 2C66, 2C67, 2C70, 2C72, 2C73, 2C75, 2C76, 2V5Z, 2V60, 2V61, 2VRL, 2VRM, 2VZ2, 2XCG, 2XFN, 2XFO, 2XFP, 2XFQ, 2XFU, 3PO7, 3ZYX, 4A79, 4A7A, 4CRT
Identifiers
Symbols	MAOB ; MGC26382
External IDs	OMIM: 309860 MGI: 96916 HomoloGene: 20251 ChEMBL: 2039 GeneCards: MAOB Gene
EC number	1.4.3.4
Gene ontology
Molecular function	• primary amine oxidase activity; • electron carrier activity; • protein homodimerization activity; • flavin adenine dinucleotide binding;
Cellular component	• mitochondrion; • mitochondrial envelope; • mitochondrial outer membrane; • mitochondrial inner membrane; • integral component of membrane; • extracellular vesicular exosome;
Biological process	• xenobiotic metabolic process; • response to toxic substance; • response to aluminum ion; • response to selenium ion; • negative regulation of serotonin secretion; • substantia nigra development; • response to lipopolysaccharide; • response to drug; • small molecule metabolic process; • response to ethanol; • positive regulation of dopamine metabolic process; • response to corticosterone; • oxidation-reduction process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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　　[★]

関: Monoamine oxidase B inhibitors

「MA」

　　[★]

「MAO」

　　[★] モノアミンオキシダーゼ monoamine oxidase

[1] "Entrez Gene: MAOB monoamine oxidase B".

[pmid17573034-2] Edmondson D, Binda C, Mattevi A (August 2007). "Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B". Arch. Biochem. Biophys. 464 (2): 269–76. doi:10.1016/j.abb.2007.05.006. PMC 1993809. PMID 17573034.

[Youdim-2004-3] Youdim M, Weinstock M (January 2004). "Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation". Neurotoxicology 25 (1–2): 243–50. doi:10.1016/S0161-813X(03)00103-7. PMID 14697899.

[Binda-2004-4] Binda C, Hubálek F, Li M, Herzig Y, Sterling J, Edmondson D et al. (March 2004). "Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class". J. Med. Chem. 47 (7): 1767–74. doi:10.1021/jm031087c. PMID 15027868.

[pmid8313400-5] Nolen W, Hoencamp E, Bouvy P, Haffmans P (1993). "Reversible monoamine oxidase-A inhibitors in resistant major depression". Clin Neuropharmacol 16 (Suppl 2): S69–76. PMID 8313400.

[pmid22110357-6] Riederer P, Laux G (March 2011). "MAO-inhibitors in Parkinson's Disease". Exp Neurobiol 20 (1): 1–17. doi:10.5607/en.2011.20.1.1. PMC 3213739. PMID 22110357.

[pmid7816197-7] Saura J, Luque J, Cesura A, Da Prada M, Chan-Palay V, Huber G et al. (September 1994). "Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography". Neuroscience 62 (1): 15–30. doi:10.1016/0306-4522(94)90311-5. PMID 7816197.

[pmid19526285-8] Mallajosyula J, Chinta S, Rajagopalan S, Nicholls D, Andersen J (October 2009). "Metabolic control analysis in a cellular model of elevated MAO-B: relevance to Parkinson's disease". Neurotox Res 16 (3): 186–93. doi:10.1007/s12640-009-9032-2. PMC 2727365. PMID 19526285.

[pmid17447416-9] Nagatsu T, Sawada M (2006). "Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson's disease: possible implications of glial cells". J. Neural Transm. Suppl. Journal of Neural Transmission. Supplementa 71 (71): 53–65. doi:10.1007/978-3-211-33328-0_7. ISBN 978-3-211-33327-3. PMID 17447416.

[pmid15247489-10] Kumar M, Andersen J (August 2004). "Perspectives on MAO-B in aging and neurological disease: where do we go from here?". Mol. Neurobiol. 30 (1): 77–89. doi:10.1385/MN:30:1:077. PMID 15247489.

[pmid19657584-11] Dlugos A, Palmer A, de Wit H (October 2009). "Negative emotionality: monoamine oxidase B gene variants modulate personality traits in healthy humans". J Neural Transm 116 (10): 1323–34. doi:10.1007/s00702-009-0281-2. PMC 3653168. PMID 19657584.

[pmid20869994-12] Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N (July 2011). "Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury". Biochim. Biophys. Acta 1813 (7): 1323–32. doi:10.1016/j.bbamcr.2010.09.010. PMC 3030628. PMID 20869994.

[pmid23581564-13] Kaludercic N, Carpi A, Nagayama T, Sivakumaran V, Zhu G, Lai E et al. (January 2014). "Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts". Antioxid. Redox Signal. 20 (2): 267–80. doi:10.1089/ars.2012.4616. PMC 3887464. PMID 23581564.

[pmid10591056-14] Shih J, Chen K (1999). "MAO-A and -B gene knock-out mice exhibit distinctly different behavior". Neurobiology (Bp) 7 (2): 235–46. PMID 10591056.

[pmid9326944-15] Grimsby J, Toth M, Chen K, Kumazawa T, Klaidman L, Adams J et al. (October 1997). "Increased stress response and beta-phenylethylamine in MAOB-deficient mice.". Nature Genetics 17 (2): 206–10. doi:10.1038/ng1097-206. PMID 9326944.

[16] Shih J, Chen K, Ridd M (1999). "Monoamine oxidase: from genes to behavior.". Annual review of neuroscience 22: 197–217. doi:10.1146/annurev.neuro.22.1.197. PMC 2844879. PMID 10202537.

[Shih_21.E2.80.9330-17] Shih J (January 2004). "Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B.". Neurotoxicology 25 (1–2): 21–30. doi:10.1016/s0161-813x(03)00112-8. PMID 14697877.

[18] Bortolato M, Godar S, Davarian S, Chen K, Shih J (December 2009). "Behavioral disinhibition and reduced anxiety-like behaviors in monoamine oxidase B-deficient mice.". Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 34 (13): 2746–57. doi:10.1038/npp.2009.118. PMC 2783894. PMID 19710633.

[pmid23082958-19] Nebbioso M, Pascarella A, Cavallotti C, Pescosolido N (December 2012). "Monoamine oxidase enzymes and oxidative stress in the rat optic nerve: age-related changes". Int J Exp Pathol 93 (6): 401–5. doi:10.1111/j.1365-2613.2012.00832.x. PMC 3521895. PMID 23082958.

[pmid8423709-20] Kitani K, Kanai S, Sato Y, Ohta M, Ivy G, Carrillo M (1993). "Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence". Life Sci. 52 (3): 281–8. doi:10.1016/0024-3205(93)90219-S. PMID 8423709.

[pmid8613523-21] Lenders J, Eisenhofer G, Abeling N, Berger W, Murphy D, Konings C et al. (February 1996). "Specific genetic deficiencies of the A and B isoenzymes of monoamine oxidase are characterized by distinct neurochemical and clinical phenotypes". J. Clin. Invest. 97 (4): 1010–9. doi:10.1172/JCI118492. PMC 507147. PMID 8613523.

[Miller-22] Miller G (January 2011). "The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity". J. Neurochem. 116 (2): 164–176. doi:10.1111/j.1471-4159.2010.07109.x. PMC 3005101. PMID 21073468.

[pmid20150659-23] Miklya I (December 2009). "[Slowing the age-induced decline of brain function with prophylactic use of (−)-deprenyl (Selegiline, Jumex). Current international view and conclusions 25 years after the Knoll's proposal]". Neuropsychopharmacol Hung (in Hungarian) 11 (4): 217–25. PMID 20150659.

[pmid15246996-24] Ukraintseva S, Arbeev K, Michalsky A, Yashin A (June 2004). "Antiaging treatments have been legally prescribed for approximately thirty years". Ann. N. Y. Acad. Sci. 1019: 64–9. doi:10.1196/annals.1297.014. PMID 15246996.

[pmid17034132-25] Novaroli L, Daina A, Favre E, Bravo J, Carotti A, Leonetti F et al. (October 2006). "Impact of species-dependent differences on screening, design, and development of MAO B inhibitors". J. Med. Chem. 49 (21): 6264–72. doi:10.1021/jm060441e. PMID 17034132.

[pmid12443774-26] Carotti A, Carrieri A, Chimichi S, Boccalini M, Cosimelli B, Gnerre C et al. (December 2002). "Natural and synthetic geiparvarins are strong and selective MAO-B inhibitors. Synthesis and SAR studies". Bioorg. Med. Chem. Lett. 12 (24): 3551–5. doi:10.1016/S0960-894X(02)00798-9. PMID 12443774.

[pmid9832350-27] Uebelhack R, Franke L, Schewe H (September 1998). "Inhibition of platelet MAO-B by kava pyrone-enriched extract from Piper methysticum Forster (kava-kava)". Pharmacopsychiatry 31 (5): 187–92. doi:10.1055/s-2007-979325. PMID 9832350.

[pmid17824599-28] Leonetti F, Capaldi C, Pisani L, Nicolotti O, Muncipinto G, Stefanachi A et al. (October 2007). "Solid-phase synthesis and insights into structure-activity relationships of safinamide analogues as potent and selective inhibitors of type B monoamine oxidase". Journal of Medicinal Chemistry 50 (20): 4909–16. doi:10.1021/jm070725e. PMID 17824599.

[pmid16759116-29] und #2d, Frédérick R, Dumont W, Ooms F, Aschenbach L, Van der Schyf C, Castagnoli N et al. (June 2006). "Synthesis, structural reassignment, and biological activity of type B MAO inhibitors based on the 5H-indeno[1,2-c]pyridazin-5-one core". J. Med. Chem. 49 (12): 3743–7. doi:10.1021/jm051091j. PMID 16759116.

[pmid17910428-30] Carotti A, Catto M, Leonetti F, Campagna F, Soto-Otero R, Méndez-Alvarez E et al. (November 2007). "Synthesis and monoamine oxidase inhibitory activity of new pyridazine-, pyrimidine- and 1,2,4-triazine-containing tricyclic derivatives". Journal of Medicinal Chemistry 50 (22): 5364–71. doi:10.1021/jm070728r. PMID 17910428.

[pmid19378991-31] Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F et al. (May 2009). "Chalcones: a valid scaffold for monoamine oxidases inhibitors". J. Med. Chem. 52 (9): 2818–24. doi:10.1021/jm801590u. PMID 19378991.

[pmid12620068-32] und #21, Silvestri R, La Regina G, De Martino G, Artico M, Befani O, Palumbo M et al. (March 2003). "Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B". J. Med. Chem. 46 (6): 917–20. doi:10.1021/jm0256124. PMID 12620068.

[pmid20715818-33] und # (R)-8b, Chimenti F, Secci D, Bolasco A, Chimenti P, Granese A, Carradori S et al. (September 2010). "Synthesis, stereochemical separation, and biological evaluation of selective inhibitors of human MAO-B: 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines". J. Med. Chem. 53 (17): 6516–20. doi:10.1021/jm100120s. PMID 20715818.

[pmid17253676-34] und #18, Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A et al. (February 2007). "Selective inhibitory activity against MAO and molecular modeling studies of 2-thiazolylhydrazone derivatives". J. Med. Chem. 50 (4): 707–12. doi:10.1021/jm060869d. PMID 17253676.

[pmid17266193-35] und #3g, Chimenti F, Fioravanti R, Bolasco A, Manna F, Chimenti P, Secci D et al. (February 2007). "Monoamine oxidase isoform-dependent tautomeric influence in the recognition of 3,5-diaryl pyrazole inhibitors". J. Med. Chem. 50 (3): 425–8. doi:10.1021/jm060868l. PMID 17266193.

[pmid16279769-36] und #(S)-1, Chimenti F, Maccioni E, Secci D, Bolasco A, Chimenti P, Granese A et al. (November 2005). "Synthesis, molecular modeling studies, and selective inhibitory activity against monoamine oxidase of 1-thiocarbamoyl-3,5-diaryl-4,5-dihydro-(1H)- pyrazole derivatives". J. Med. Chem. 48 (23): 7113–22. doi:10.1021/jm040903t. PMID 16279769.

[pmid21377879-37] Mishra N, Sasmal D (April 2011). "Development of selective and reversible pyrazoline based MAO-B inhibitors: virtual screening, synthesis and biological evaluation". Bioorg. Med. Chem. Lett. 21 (7): 1969–73. doi:10.1016/j.bmcl.2011.02.030. PMID 21377879.

[pmid16884303-38] und #41, Catto M, Nicolotti O, Leonetti F, Carotti A, Favia A, Soto-Otero R et al. (2006). "Structural insights into monoamine oxidase inhibitory potency and selectivity of 7-substituted coumarins from ligand- and target-based approaches". Journal of Medicinal Chemistry 49 (16): 4912–25. doi:10.1021/jm060183l. PMID 16884303.

[pmid21684743-39] und #2, Matos M, Vazquez-Rodriguez S, Uriarte E, Santana L, Viña D (July 2011). "MAO inhibitory activity modulation: 3-Phenylcoumarins versus 3-benzoylcoumarins". Bioorg. Med. Chem. Lett. 21 (14): 4224–7. doi:10.1016/j.bmcl.2011.05.074. PMID 21684743.

[pmid20659799-40] Matos M, Viña D, Janeiro P, Borges F, Santana L, Uriarte E (September 2010). "New halogenated 3-phenylcoumarins as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 20 (17): 5157–60. doi:10.1016/j.bmcl.2010.07.013. PMID 20659799.

[pmid19628387-41] Matos M, Viña D, Picciau C, Orallo F, Santana L, Uriarte E (September 2009). "Synthesis and evaluation of 6-methyl-3-phenylcoumarins as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 19 (17): 5053–5. doi:10.1016/j.bmcl.2009.07.039. PMID 19628387.

[pmid19423346-42] Matos M, Viña D, Quezada E, Picciau C, Delogu G, Orallo F et al. (June 2009). "A new series of 3-phenylcoumarins as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 19 (12): 3268–70. doi:10.1016/j.bmcl.2009.04.085. PMID 19423346.

[pmid21194943-43] und #9, #12, Gaspar A, Reis J, Fonseca A, Milhazes N, Viña D, Uriarte E et al. (January 2011). "Chromone 3-phenylcarboxamides as potent and selective MAO-B inhibitors". Bioorg. Med. Chem. Lett. 21 (2): 707–9. doi:10.1016/j.bmcl.2010.11.128. PMID 21194943.

[pmid21134756-44] und #9i, Manley-King C, Bergh J, Petzer J (January 2011). "Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues". Bioorg. Med. Chem. 19 (1): 261–74. doi:10.1016/j.bmc.2010.11.028. PMID 21134756.

[pmid21778064-45] und #5c, Manley-King C, Bergh J, Petzer J (August 2011). "Inhibition of monoamine oxidase by C5-substituted phthalimide analogues". Bioorg. Med. Chem. 19 (16): 4829–40. doi:10.1016/j.bmc.2011.06.070. PMID 21778064.

[pmid21621312-46] Strydom B, Bergh J, Petzer J (August 2011). "8-Aryl- and alkyloxycaffeine analogues as inhibitors of monoamine oxidase". Eur J Med Chem 46 (8): 3474–85. doi:10.1016/j.ejmech.2011.05.014. PMID 21621312.

[pmid20093036-47] Strydom B, Malan S, Castagnoli N, Bergh J, Petzer J (February 2010). "Inhibition of monoamine oxidase by 8-benzyloxycaffeine analogues". Bioorg. Med. Chem. 18 (3): 1018–28. doi:10.1016/j.bmc.2009.12.064. PMID 20093036.

[pmid16442801-48] Vlok N, Malan S, Castagnoli N, Bergh J, Petzer J (May 2006). "Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC)". Bioorg. Med. Chem. 14 (10): 3512–21. doi:10.1016/j.bmc.2006.01.011. PMID 16442801.

[pmid18723354-49] Pretorius J, Malan S, Castagnoli N, Bergh J, Petzer J (September 2008). "Dual inhibition of monoamine oxidase B and antagonism of the adenosine A(2A) receptor by (E,E)-8-(4-phenylbutadien-1-yl)caffeine analogues". Bioorganic & Medicinal Chemistry 16 (18): 8676–84. doi:10.1016/j.bmc.2008.07.088. PMID 18723354.

[50] Tzvetkov et al. (2014): "Indazole- and Indole-5-carboxamides: Selective and Reversible Monoamine Oxidase B Inhibitors with Subnanomolar Potency". Journal of Medicinal Chemistry. epub.

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