Monoamine oxidase and α-synuclein as targets in Parkinson's disease therapy

Expert Review of Neurotherapeutics

Volumn 14, Issue 6, 2014, Pages 703-716

  Follmer, Cristian ^a  

^a FEDERAL UNIVERSITY OF RIO DE JANEIRO   (Brazil)

Author keywords

dopamine; fibrils; monoamine oxidase; oxidative stress; Parkinson's disease; protofibrils; synuclein

Indexed keywords

ALDEHYDE DEHYDROGENASE; ALPHA SYNUCLEIN; AMINE OXIDASE (FLAVIN CONTAINING); AMYLOID BETA PROTEIN; AMYLOID PROTEIN; APIGENIN; BROMOCRIPTINE; CATECHIN; CATECHOL; CHRYSIN; CURCUMIN; DOPAMINE; EPICATECHIN; GINKGO BILOBA EXTRACT; HYDROGEN PEROXIDE; KAEMPFEROL; LEVODOPA; MELATONIN; MONOAMINE OXIDASE INHIBITOR; NATURAL PRODUCT; NORADRENALIN; PERGOLIDE; PRION PROTEIN; PROSTAGLANDIN G2; PROSTAGLANDIN H2; QUERCETIN; SELEGILINE; SEROTONIN; SNARE PROTEIN;

CATECHOLAMINE METABOLISM; ENZYME INACTIVATION; HUMAN; NONHUMAN; OXIDATION; OXIDATIVE STRESS; PARKINSON DISEASE; REVIEW; DOPAMINERGIC NERVE CELL; DRUG EFFECTS; METABOLISM;

ALPHA-SYNUCLEIN; DOPAMINERGIC NEURONS; HUMANS; MONOAMINE OXIDASE; MONOAMINE OXIDASE INHIBITORS; PARKINSON DISEASE;

EID: 84901466063     PISSN: 14737175     EISSN: 17448360     Source Type: Journal    
DOI: 10.1586/14737175.2014.920235     Document Type: Review

References (121)

1. Langston JW. The Parkinson's complex: parkinsonism is just the tip of the iceberg. Ann Neurol 2006;59:591-6
2. Langston JW, Ballard P, Tetrud JW, et al. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983;219:979-80
3. Sulzer D. Multiple hit hypotheses for dopamine neuron loss in Parkinson's disease. Trends Neurosci 2007;30:244-50
4. Sian J, Dexter DT, Lees AJ, et al. Alterations in glutathione levels in Parkinson's disease and other neurodegenerative disorders affecting basal ganglia. Ann Neurol 1994;36:348-55
5. Martignoni E, Blandini F, Godi L, et al. Peripheral markers of oxidative stress in Parkinson's disease. The role of L-DOPA. Free Radic Biol Med 1999;27:428-37
6. Buhmann C, Arlt S, Kontush A, et al. Plasma and CSF markers of oxidative stress are increased in Parkinson's disease and influenced by antiparkinsonian medication. Neurobiol Dis 2004;15:160-70
7. Spillantini MG, Crowther RA, Jakes R, et al. Alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc Natl Acad Sci USA 1998;95:6469-73
8. Androulidakis AG, Kühn AA, Chen CC, et al. Dopaminergic therapy promotes lateralized motor activity in the subthalamic area in Parkinson's disease. Brain 2007;130: 457-68
9. Youdim MB, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat Rev Neurosci 2006;7:295-309
10. Bach AW, Lan NC, Johnson DL, et al. cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci USA 1988;85:4934-8
11. Johnston JP. Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem Pharmacol 1968;17: 1285-97
12. Binda C, Newton-Vinson P, Hubálek F, et al. Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders. Nat Struct Biol 2002;9:22-6
13. Javitch JA, D'Amato RJ, Strittmatter SM, et al. Parkinsonism-inducing neurotoxin, Nmethyl-4-phenyl-1,2,3,6-tetrahydropyri-dine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 1985;82:2173-7
14. Youdim MBH, Finberg JPM, Tipton KF. In: Trendelenburg U, Weiner N, editors. Catecholamines. II: handbook of experimental pharmacology. Springer; Berlin: 1998. p. 127-99
15. Fowler JS, Volkow ND, Wang GJ, et al. Age-related increases in brain MAO B in healthy human subjects. Neurobiol Aging 1997;18:431-5
16. Saura J, Luque JM, Cesura AM, et al. Increased monoamine oxidase B activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography. Neuroscience 1994;62: 15-30
17. Pålhagen S, Heinonen E, Hägglund J, et al. Swedish Parkinson Study Group. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology 2006;66: 1200-6
18. Olanow CW, Hauser RA, Gauger L, et al. The effect of deprenyl and levodopa on the progression of Parkinson's disease. Ann Neurol 1995;38:771-7
19. Maruyama W, Takahashi T, Naoi M. (-)-Deprenyl protects human dopaminergic neuroblastoma SH-SY5Y cells from apoptosis induced by peroxynitrite and nitric oxide. J Neurochem 1998;70:2510-15
20. Braga CA, Follmer C, Palhano FL, et al. The anti-parkinsonian drug selegiline delays the nucleation phase of a-synuclein aggregation leading to the formation of nontoxic species. J Mol Biol 2011;405: 254-73
21. Spillantini MG, Schmidt ML, Lee VM, et al. Alpha-synuclein in Lewy bodies. Nature 1997;388:839-40
22. Wakabayashi K, Yoshimoto M, Fukushima T, et al. Widespread occurrence of alpha-synuclein/NACP-immunoreactive neuronal inclusions in juvenile and adult-onset Hallervorden-Spatz disease with Lewy bodies. Neuropathol Appl Neurobiol 1999;225:363-8
23. Wakabayashi K, Yoshimoto M, Tsuji S, et al. Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. Neuroscience 1998;249: 180-2
24. Baba M, Nakajo S, Tu PH, et al. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies. Am J Pathol 1998;152:879-84
25. Lippa SM, Lippa CF, Mori H. Alpha-synuclein aggregation in pathological aging and Alzheimer's disease: the impact of beta-amyloid plaque level. Am J Alzheimers Dis Other Demen 2005;20:315-18
26. Lippa CF, Fujiwara H, Mann DM, et al. Lewy bodies contain altered alpha-synuclein in brains of many familial Alzheimeŕs disease patients with mutations in preselin and amyloid precursor protein genes. Am J Pathol 1998;153:1365-70
27. Burke WJ, Li SW, Williams EA, et al. 3,4-Dihydroxyphenylacetaldehyde is the toxic dopamine metabolite in vivo: implications for Parkinson's disease pathogenesis. Brain Res 2003;989:205-13
28. Shen HM, Liu ZG. JNK signaling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med 2005;40:928-39
29. Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 2012;24:981-90
30. Sulzer D, Zecca L. Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 2000;1:81-195
31. Teismann P, Tieu K, Choi DK, et al. Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration. Proc Natl Acad Sci USA 2003;100:5473-8
32. Zigler JS Jr, Jernigan HM Jr, Garland D, et al. The effects of "oxygen radicals" generated in the medium on lenses in organ culture: inhibition of damage by chelated iron. Arch Biochem Biophys 1985;241: 163-72
33. Jellinger K, Paulus W, Grundke-Iqbal I, et al. Brain iron and ferritin in Parkinson's and Alzheimer's diseases. J Neural Transm Park Dis Dement Sect 1990;2:327-40
34. Anderson DG, Mariappan SV, Buettner GR, et al. Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone. J Biol Chem 2011;286:26978-86
35. Galter D, Buervenich S, Carmine A, et al. ALDH1 mRNA: presence in human dopamine neurons and decreases in substantia nigra in Parkinson's disease and in the ventral tegmental area in schizophrenia. Neurobiol Dis 2003;14: 637-47
36. Michel TM, Käsbauer L, Gsell W, et al. Aldehyde dehydrogenase 2 in sporadic Parkinson's disease. Parkinsonism Relat Disord 2014;20:68-72
37. Mizuno Y, Ohta S, Tanaka M, et al. Deficiencies in complex I subunits of the respiratory chain in Parkinson's disease. Biochem Biophys Res Commun 1989;163: 1450-5
38. Lamensdorf I, Eisenhofer G, Harvey-White J, et al. Metabolic stress in PC12 cells induces the formation of the endogenous dopaminergic neurotoxin, 3,4-dihydroxyphenylacetaldehyde. J Neurosci Res 2000;60:552-8
39. Burke WJ, Li SW, Schmitt CA, et al. Accumulation of 3,4- dihydroxyphenylglycolaldehyde, the neurotoxic monoamine oxidase A metabolite of norepinephrine, in locus coeruleus cell bodies in Alzheimer's disease: mechanism of neuron death. Brain Res 1999;816:633-7
40. Zellner M, Baureder M, Rappold E, et al. Comparative platelet proteome analysis reveals an increase of monoamine oxidase-B protein expression in Alzheimer's disease but not in non-demented Parkinson's disease patients. J Proteomics 2012;75:2080-92
41. Guay DR. Rasagiline (TVP-1012): a new selective monoamine oxidase inhibitor for Parkinson's disease. Am J Geriatr Pharmacother 2006;4:330-46
42. Youdim MB, Weinstock M. Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyramine potentiation. Neurotoxicology 2004;25: 243-50
43. Nagatsu T, Sawada M. 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 2006;71:53-65
44. Lippman SB, Nash K. Monoamine oxidase inhibitor update. Potential adverse food and drug interactions. Drug Saf 1990;5:195-204
45. Weinstock M, Gorodetsky E, Wang RH, et al. Limited potentiation of blood pressure response to oral tyramine by brain-selective monoamine oxidase A-B inhibitor, TV-3326 in conscious rabbits. Neuropharmacology 2002;43:999-1005
46. Cohen G, Pasik P, Cohen B, et al. Pargyline and deprenyl prevent the neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in monkeys. Eur J Pharmacol 1984;106: 209-10
47. Di Monte DA, DeLanney LE, Irwin I, et al. Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of L-DOPA-treated monkeys. Brain Res 1996;738:53-9
48. Riederer P, Youdim MB. Monoamine oxidase activity and monoamine metabolism in brains of parkinsonian patients treated with l-deprenyl. J Neurochem 1986;46: 1359-65
49. Chiueh CC, Huang SJ, Murphy DL. Suppression of hydroxyl radical formation by MAO inhibitors: a novel possible neuroprotective mechanism in dopaminergic neurotoxicity. J Neural Transm Suppl 1994;41:189-96
50. Tolbert SR, Fuller MA. Selegiline in treatment of behavioral and cognitive symptoms of Alzheimer disease. Ann Pharmacother 1996;30:1122-9
51. Grandinetti A, Morens DM, Reed D, et al. Prospective study of cigarette smoking and the risk of developing idiopathic Parkinson's disease. Am J Epidemiol 1994;139:1129-38
52. Fowler JS, Volkow ND, Wang GJ, et al. Inhibition of monoamine oxidase B in the brains of smokers. Nature 1996;379:733-6
53. Palomo T, Kostrzewa RM, Beninger RJ, et al. Gene-environment interplay in alcoholism and other substance abuse disorders: expressions of heritability and factors influencing vulnerability. Neurotox Res 2004;6:343-61
54. Herraiz T, Chaparro C. Human monoamine oxidase is inhibited by tobacco smoke: beta-carboline alkaloids act as potent and reversible inhibitors. Biochem Biophys Res Commun 2005;326:378-86
55. Rommelspacher H. The beta-carbolines (harmanes)-a new class of endogenous compounds: their relevance for the pathogenesis and treatment of psychiatric and neurological diseases. Pharmacopsychiatria 1981;14:117-25
56. Cao R, Peng W, Wang Z, et al. Beta-Carboline alkaloids: biochemical and pharmacological functions. Curr Med Chem 2007;14:479-500
57. Herraiz T. Evaluation of the oxidation of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) to toxic pyridinium cations by monoamine oxidase (MAO) enzymes and its use to search for new MAO inhibitors and protective agents. J Enzyme Inhib Med Chem 2012;27:810-17
58. Herraiz T, Chaparro C. Human monoamine oxidase enzyme inhibition by coffee and beta-carbolines norharman and harman isolated from coffee. Life Sci 2006;78:795-802
59. Ross GW, Abbott RD, Petrovitch H, et al. Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 2000;283:2674-9
60. Khalil AA, Steyn S, Castagnoli N. Isolation and characterization of a monoamine oxidase inhibitor from tobacco leaves. Chem Res Toxicol 2000;13:31-5
61. Castagnoli KP, Steyn SJ, Petzer JP, et al. Neuroprotection in the MPTP Parkinsonian C57BL/6 mouse model by a compound isolated from tobacco. Chem Res Toxicol 2001;14:523-7
62. Coelho-Cerqueira E, Netz PA, Diniz C, et al. Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO. Bioorg Med Chem 2011;19:7416-24
63. Thomson RH. Naturally occurring quinones. Springer; London: 1996
64. Jäger AK, Saaby L. Flavonoids and the CNS. Molecules 2011;16:1471-85
65. Dixon Clarke SE, Ramsay RR. Dietary inhibitors of monoamine oxidase A. J Neural Transm 2011;118:1031-41
66. Yoshino S, Hara A, Sakakibara H, et al. Effect of quercetin and glucuronide metabolites on the monoamine oxidase-A reaction in mouse brain mitochondria. Nutrition 2011;27:847-52
67. Xu Y, Lin D, Li S, et al. Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress. Neuropharmacology 2009;57:463-71
68. Rajeswari A, Sabesan M. 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. Inflammopharmacology 2008;16:96-9
69. Hamaguchi T, Ono K, Yamada M. REVIEW: curcumin and Alzheimer's disease. CNS Neurosci Therap 2010;16: 285-97
70. Sloley BD, Urichuk LJ, Morley P, et al. Identification of kaempferol as a monoamine oxidase inhibitor and potential Neuroprotectant in extracts of Ginkgo biloba leaves. J Pharm Pharmacol 2000;52: 451-9
71. Fink AL. The aggregation and fibrillation of alpha-synuclein. Acc Chem Res 2006;39: 628-34
72. Polymeropoulos MH, Lavedan C, Leroy E, et al. Mutation in the a-synuclein gene identified in families with Parkinson's disease. Science 1997;276:2045-7
73. Zarranz JJ, Alegre J, Gómez-Esteban JC, et al. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol 2004;55: 164-73
74. Fauvet B, Mbefo MK, Fares MB, et al. Alpha-synuclein in the central nervous system and from erythrocytes, mammalian cells and E. coli exists predominantly as a disordered monomer. J Biol Chem 2012;287:15345-64
75. Bartels T, Choi JG, Selkoe DJ. a-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation. Nature 2011;477:107-10
76. Coelho-Cerqueira E, Carmo-Gonçalves P, Pinheiro A, et al. a-Synuclein as an intrinsically disordered monomer-fact or artefact? FEBS J 2013;280:4915-27
77. Burré J, Vivona S, Diao J, et al. Properties of native brain a-synuclein. Nature 2013;498:E4-6
78. Hasegawa M, Fujiwara H, Nonaka T, et al. Phosphorylated alpha-synuclein is ubiquitinated in alpha-synucleinopathy lesions. J Biol Chem 2002;277:49071-6
79. Muntané G, Dalfó E, Martinez A, Ferrer I. Phosphorylation of tau and alpha-synuclein in synaptic-enriched fractions of the frontal cortex in Alzheimer's disease, and in Parkinson's disease and related alpha-synucleinopathies. Neuroscience 2008;152:913-23
80. Burré J, Sharma M, Tsetsenis T, et al. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 2010;329:1663-7
81. Lashuel HA, Hartley D, Petre BM, et al. Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 2002;418:291
82. Winner B, Jappelli R, Maji SK, et al. In vivo demonstration that alpha-synuclein oligomers are toxic. Proc Natl Acad Sci USA 2011;108:4194-9
83. Masliah E, Rockenstein E, Veinbergs I, et al. Dopaminergic loss and inclusion body formation in alpha-synuclein mice: implications for neurodegenerative disorders. Science 2000;287:1265-9
84. Karpinar DP, Balija MB, Kügler S, et al. Pre-fibrillar alpha-synuclein variants with impaired beta-structure increase neurotoxicity in Parkinson's disease models. EMBO J 2009;28:3256-68
85. Feany MB, Bender WW. A. Drosophila model of Parkinson's disease. Nature 2000;404:394-8
86. Kirik D, Rosenblad C, Burger C, et al. Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system. J Neurosci 2002;22:2780-91
87. Kirik D, Annett LE, Burger C, et al. Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson's disease. Proc Natl Acad Sci USA 2003;100:2884-9
88. Volpicelli-Daley LA, Luk KC, Patel TP, et al. Exogenous a-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 2011;72:57-71
89. Yonetani M, Nonaka T, Masuda M, et al. Conversion of wild-type alpha-synuclein into mutant-type fibrils and its propagation in the presence of A30P mutant. J Biol Chem 2009;284:7940-50
90. Tanaka M, Collins SR, Toyama BH, Weissman JS. The physical basis of how prion conformations determine strain phenotypes. Nature 2006;442:585-9
91. Burré J, Sharma M, Südhof TC. Systematic mutagenesis of a-synuclein reveals distinct sequence requirements for physiological and pathological activities. J Neurosci 2012;32: 15227-42
92. Hasegawa T, Matsuzaki-Kobayashi M, Takeda A, et al. Alpha-synuclein facilitates the toxicity of oxidized catechol metabolites: implications for selective neurodegeneration in Parkinson's disease. FEBS Lett 2006;580: 2147-52
93. Conway KA, Rochet JC, Bieganski RM, Lansbury PT Jr. Kinetic stabilization of the alpha-synuclein protofibril by a dopamine-alpha-synuclein adduct. Science 2001;294:1346-9
94. Leong SL, Pham CL, Galatis D, et al. Formation of dopamine-mediated alpha-synuclein-soluble oligomers requires methionine oxidation. Free Radic Biol Med 2009;46:1328-37
95. Nakaso K, Tajima N, Ito S, et al. Dopamine-mediated oxidation of methionine 127 in a-synuclein causes cytotoxicity and oligomerization of a-synuclein. PLoS One 2003;8:e55068
96. Follmer C, Romão L, Einsiedler CM, et al. Dopamine affects the stability, hydration and packing of protofibrils and fibrils of wild-type and variants of a-synuclein. Biochemistry 2007;46:472-82
97. Burke WJ, Kumar VB, Pandey N, et al. Aggregation of alpha-synuclein by DOPAL, the monoamine oxidase metabolite of dopamine. Acta Neuropathol 2008;115: 193-203
98. Ono K, Hasegawa K, Naiki H, Yamada M. Anti-parkinsonian agents have anti-amyloidogenic activity for Alzheimeŕs b-amyloid fibrils in vitro. Neurochem Int 2006;48:275-85
99. Ono K, Hirohata M, Yamada M. Anti-fibrillogenic and fibril-destabilizing activities of anti-Parkinsonian agents for alpha-synuclein fibrils in vitro. J Neurosci Res 2007;85:1547-57
100. Ono K, Yamada M. Antioxidant compounds have potent anti-fibrillogenic and fibril-destabilizing effects for alpha-synuclein fibrils in vitro. J Neurochem 2006;97:105-15
101. Ono K, Mochizuki H, Ikeda T, et al. Effect of melatonin on a-synuclein self-assembly and cytotoxicity. Neurobiol Aging 2012;33: 2172-85
102. Hirohata M, Ono K, Morinaga A, et al. Anti-aggregation and fibril-destabilizing effects of sex hormones on alpha-synuclein fibrils in vitro. 2009;217:434-9
103. Ono K, Yamada M. Vitamin A potently destabilizes preformed alpha-synuclein fibrils in vitro: implications for Lewy body diseases. Neurobiol Dis 2007;25:446-54
104. Silva FL, Coelho-Cerqueira E, Freitas MS, et al. Vitamins K interact with N-terminus a-synuclein and modulate the protein fibrillization in vitro. Exploring the interaction between quinones and a-synuclein. Neurochem Int 2013;62: 103-12
105. Di Giovanni S, Eleuteri S, Paleologou KE, et al. Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity. J Biol Chem 2010;285:14941-54
106. Zhu M, Rajamani S, Kaylor J, et al. The flavonoid baicalein inhibits fibrillation of alpha-synuclein and disaggregates existing fibrils. J Biol Chem 2004;279:26846-57
107. Li HT, Lin DH, Luo XY, et al. Inhibition of alpha-synuclein fibrillation by dopamine analogs via reaction with the amino groups of alpha-synuclein. Implication for dopaminergic neurodegeneration. FEBS J 2005;272:3661-72
108. Männistö PT, Tuomainen P, Tuominen RK. Different in vivo properties of three new inhibitors of catechol O-methyltransferase in the rat. Br J Pharmacol 1992;105:569-74
109. Ahmad B, Lapidus LJ. Curcumin prevents aggregation in a-synuclein by increasing reconfiguration rate. J Biol Chem 2012;287: 9193-9
110. Pandey N, Strider J, Nolan WC, et al. Curcumin inhibits aggregation of alpha-synuclein. Acta Neuropathol 2008;115:479-89
111. Wang MS, Boddapati S, Emadi S, Sierks MR. Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model. BMC Neurosci 2010;11:57
112. Liu Z, Yu Y, Li X, et al. Curcumin protects against A53T alpha-synuclein-induced toxicity in a PC12 inducible cell model for Parkinsonism. Pharmacol Res 2011;63: 439-44
113. Ono K, Yoshiike Y, Takashima A, et al. Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease. J Neurochem 2003;87:172-81
114. Hou WC, Lin RD, et al. Monoamine oxidase B (MAO-B) inhibition by active principles from Uncaria rhynchophylla. J Ethnopharmacol 2005;100:216-20
115. Johnston TH, Brotchie JM. Drugs in development for Parkinson's disease: an update. Curr Opin Investig Drugs 2006;7:25-32
116. Dalpiaz A, Cacciari B, Vicentini CB, et al. A novel conjugated agent between dopamine and an A2A adenosine receptor antagonist as a potential anti-Parkinson multitarget approach. Mol Pharm 2012; 9(3):591-604
117. Gal S, Zheng H, Fridkin M, Youdim MB. Restoration of nigrostriatal dopamine neurons in post-MPTP treatment by the novel multifunctional brain-permeable iron chelator-monoamine oxidase inhibitor drug, M30. Neurotox Res 2010;17:15-27
118. Youdim MB, Fridkin M, Zheng H. Bifunctional drug derivatives of MAO-B inhibitor rasagiline and iron chelator VK-28 as a more effective approach to treatment of brain ageing and ageing neurodegenerative diseases. Mech Ageing Dev 2005;126:317-26
119. Youdim MB. Multi target neuroprotective and neurorestorative anti-Parkinson and anti-Alzheimer drugs ladostigil and m30 derived from rasagiline. Exp Neurobiol 2013;22:1-10
120. Geha RM, Rebrin I, Chen K, Shih JC. Substrate and inhibitor specificities for human monoamine oxidase A and B are influenced by a single amino acid. J Biol Chem 2001;276:9877-82
121. Han XH, Hong SS, Hwang JS, et al. Monoamine oxidase inhibitory components from Cayratia japonica. Arch Pharm Res 2007;30:13-17