Skip to main content
SpringerLink
Log in

Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson’s Disease

  • Living reference work entry
  • Latest version View entry history
  • First Online:
NeuroPsychopharmacotherapy

Abstract

Monoamine oxidases (MAO)-A and MAO-B catalyze the oxidative deamination of monoamine neurotransmitters, such as dopamine (DA), noradrenaline, and serotonin, in the central and peripheral nervous system. Parkinson’s disease (PD) is an aging-related movement disorder, caused by a deficiency of the neurotransmitter DA in the striatum of the brain, caused by degeneration of the nigrostriatal DA neurons. During the1960s, L-DOPA, a direct precursor of DA, which is synthesized in vivo from tyrosine in DA neurons by tyrosine hydroxylase and is converted to DA by aromatic L-amino acid decarboxylase, was introduced to treat this DA deficiency in the striatum. In addition to L-DOPA as a treatment, MAO-B inhibitors (MAO-B-Is) have been used since the 1970s, first selegiline (L-(-)-deprenyl), then rasagiline, and more recently safinamide, as an effective therapy for PD by preventing the degradation of DA. Furthermore, monotherapy with MAO-B-I, selegiline, rasagiline, or safinamide has been proved to be effective in the case of early PD. Accumulating data suggest that MAO-B-Is may also have neuroprotective efficacy due to several mechanisms that may or may not be related to MAO inhibition. DA oxidation and formation of misfolded α-synuclein oligomers may be linked to dysfunctions of mitochondria, the autophagy-lysosomal system, and ubiquitin-proteasome system, resulting in DA neuron death in PD; and MAO-I may prevent these processes to afford neuroprotection. However, many clinical and basic studies have suggested, but not yet convincingly proved, neuroprotective effects of MAO-I in PD. It remains to be proved if the administration of MAO-B-I several decades before the onset of PD could prevent the occurrence of PD based on neuroprotection and, if so, to confirm the molecular mechanism involved.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AADC:

Aromatic L-amino acid decarboxylase

ALDH:

Aldehyde dehydrogenase

DA:

Dopamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

DOPAL:

3,4-Dihydroxyphenylacetaldehyde

L-DOPA:

L-3,4-Dihydroxyphenylalanine/levodopa

MAO:

Monoamine oxidase

MAO-I:

MAO inhibitor

MPP+:

1-Methyl-4-phenyl-pyridinium

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

TH:

Tyrosine hydroxylase

VMAT2:

Vesicular monoamine transporter 2

References

  • Allain H, Pollak P, Neukirch HC. Members of the French Selegiline multicenter trial. Symptomatic effect of selegiline in de novo Parkinsonian patients. Mov Disord. 1993;8(Suppl 1):S36–40.

    Article  PubMed  Google Scholar 

  • Ando T, Chock PB, Murphy DL, Chiueh CC. Role of the redox protein thioredoxin in cytoprotective mechanism evoked by (-)-deprenyl. Mol Pharmacol. 2005;68:1408–14.

    Article  CAS  Google Scholar 

  • Bar-Am O, Amit T, Kupershmidt L, Aluf Y, Mechlovich D, Kabha H, Danovitch L, Zurawski VR, Youdim MB, Weinreb O. Neuroprotective and neurorestorative activities of a novel iron chelator-brain selective monoamine oxidase-A/monoamine oxidase-B inhibitor in animal models of Parkinson’s disease and aging. Neurobiol Aging. 2015;36:1529–42.

    Article  CAS  PubMed  Google Scholar 

  • Betarbet R, Sherer TB, Mackenzie G, Garcia-Osuna M, Panov AV, Greenmyre T. Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci. 2000;3:1301–6.

    Article  CAS  PubMed  Google Scholar 

  • Birkmayer W, Hornykiewicz O. The L-3,4-Dioxyphenylalanin (DOPA)-effect in Parkinson-akinesie. Wien Klin Wochenschr. 1961;73:787–8.

    CAS  PubMed  Google Scholar 

  • Birkmayer W, Riederer P, Youdim MB, Linauer W. The potential of the anti akinetic effect after L-dopa treatment by an inhibitor of MAO-B, Deprenil. J Neural Transm. 1975;36:303–26.

    Article  CAS  PubMed  Google Scholar 

  • Birkmayer W, Knoll J, Riederer P, Youdim M, Hars V, Marton A. Increased life expectancy resulting from addition of L-deprenyl to madopar® treatment in Parkinson’s disease: a long term study. J Neural Transm. 1985;64:113–27.

    Article  CAS  PubMed  Google Scholar 

  • Bonifati V, Rizzu P, van Baren MJ, Schaap OJ, Breedveld GJ, Krieger E, Dekker MCJ, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Sweten JC, Brice A, Meco G, van Duijin CM, Oostra BA, Heutink P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003;299:256–9.

    Article  CAS  PubMed  Google Scholar 

  • Braga CA, Follmer C, Palhano FL, Khattar E, Freitas MS, Romano FL, Khattar E, Freitas MS, Romão L, Giovanni SD, Lashuel HA, Silva JL, Foguel D. The anti-Parkinsonian drug selegiline delays the nucleation phase of alpha-synuclein aggregation leading to the formation of nontoxic species. J Mol Biol. 2011;405:254–73.

    Article  CAS  PubMed  Google Scholar 

  • Burbulla LF, Song P, Mazzulli R, Zampese E, Wang YC, Jeon S, Santos DP, Blanz J, Obermair CD, Strojny C, Savas JN, Kiskinis E, Zhuang X, Krüger R, Sumeier DJ, Krainc D. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease. Science. 2017; https://doi.org/10.1126/science.aam9080.

  • Casida JE, Ford B, Jinsinama Y, Sullivan P, Cooney A, Goldstein DS. Benomyl, aldehyde dehydrogenase, DOPAL, and catecholaldehyde hypothesis for the pathogenesis of Parkinson’s disease. Chem Res Toxicol. 2014;27:1359–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cereda E, Cilia R, Canesi M, Tesei S, Mariani CB, Zecchinelli AL, Pezzoli G. Efficacy of rasagiline and selegiline in Parkinson’s disease: a head-to-head 3-year retrospective case-control study. J Neurol. 2017;264:1254–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen K, Shih JC. Monoamine oxidase A and B: structure, function, and behavior. Adv Pharmacol. 1998;42:292–6.

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Xie Z, Turkson S, Zhuang X. A57T human α-synuclein overexpression in transgenic mice induces pervasive mitochondria macroautophagy defects producing dopamine neuron degeneration. J Neuirosci. 2015;35:890–905.

    Article  CAS  Google Scholar 

  • Chung JY, Lee JW, Ryu CH, Min HK, Yoon YJ, Lim MJ, Park CH. 1-[2-(4-Benzyloxyphenoxy)ethyl]imidazole inhibits monoamine oxidase B and protects against neuronal loss and behavioral impairment in rodent model of Parkinson’s disease. J Neurosci Res. 2015;93:1267–78.

    Article  CAS  PubMed  Google Scholar 

  • Collins MA, Neafsey EJ. Beta-carboline analogues of N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP): endogenous factors underlying idiopathic parkinsonism? Neurosci Lett. 1985;55:179–84.

    Google Scholar 

  • Collins MA, Neafsey EJ. Beta-carboline analogues of MPP+ as environmental neurotoxins. In: Storch A, Collins MA, editors. Neurotoxic factors in Parkinson’s disease and related disorders. New York: Kluwer Academic Publishing/Plenum; 2000. p. 115–30.

    Chapter  Google Scholar 

  • Cotzias GC, Papavasiliou PS, Gellene R. Modification of parkinsonism – chronic treatment with L-DOPA. N Engl J Med. 1969;280:337–45.

    Article  CAS  PubMed  Google Scholar 

  • Danielson SR, Held JM, Schilling B, Oo M, Gibson BW, Anderson JK. Preferentially increased nitration of alpha-synuclein at tyrosine-39 in a cellular oxidative model of Parkinson’ disease. Anal Chem. 2009;81:7823–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dexter DT, Wells FR, Agid F, Agid Y, Lees AJ, Jenner P, Marsden CD. Increased nigral iron content in postmortem parkinsonian brain. Lancet. 1987;330:1219–20.

    Article  Google Scholar 

  • Ehringer H, Hornykiewicz O. Verteilung von Noradrenalin und Dopamin (3-Hydroxytyramin) im Gehirn des Menschen und ihr Verhalten bei Erkrankungen des Extrapyramidalen Systems. Klin Wochenschr. 1960;38:1236–9.

    Article  CAS  PubMed  Google Scholar 

  • Fahn S. The medical treatment of Parkinson disease from James Parkinson to George Cotzias. Mov Disord. 2015;30:331–49.

    Google Scholar 

  • Fitzmaurice AG, Rhodes SL, Lulla A, Murphy NP, Lam HA, O’Donnel KC, Bamhill L, Casida JE, Cockbaurn M, Segasti A, Stahl MC, Maidment NT, Ritz B. Aldehyde dehydrogenase inhibition as a pathogenic mechanism in Parkinson disease. Prod Natl Acad Sci USA. 2013;110:636–41.

    Article  CAS  Google Scholar 

  • Fowler JS, Volkow ND, Wang GJ, Pappas N, Shea C, MacGregor RR. Visualization of monoamine oxidase in human brain. Adv Pharmacol. 1998;42:304–7.

    Article  CAS  PubMed  Google Scholar 

  • Goldstein DS, Holmes C, Kopin IJ, Sharabi Y. Intraneuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases. J Clin Invest. 2011;121:3320–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstein DS, Sullivan P, Holmes C, Miller GW, Alter S, Strong R, Mash DC, Kopin IJ, Sharabi Y. Determination of the toxic dopamine metabolite DOPAL in Parkinson’s disease. J Neurochem. 2013;126:591–603.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstein DS, Jinsmaa Y, Sullivan P, Holmes C, Kopin IJ, Sharabi Y. Comparison of monoamine oxidase inhibitors in decreasing production of the autotoxic dopamine metabolite 3,4-dihydorxyphenylactaldehyde in PC 12 cells. J Pharmacol Exp Therap. 2016;356:483–92.

    Article  CAS  Google Scholar 

  • Grünblatt E, Riederer P. Aldehyde dehydrogenase (ALDH) in Alzheimer’s and Parkinson’s disease. J Neutral Transm. 2016;123:83–90.

    Article  CAS  Google Scholar 

  • Hara MR, Thomas B, Cascio MB, Bae B, Hester LD, Dawson VL, Dawson TM, Sawa A, Snyder S. Neuroprotection by pharmacologic blockade of the GAPDH death signal. Proc Natl Acad Sci USA. 2006;103:3887–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hattori N, Mizuno Y. Twenty years since the discovery of the parkin gene. J Neural Transm. 2017;124:1037–54.

    Article  CAS  PubMed  Google Scholar 

  • Hauser RA, Li R, Pérez A, Ren X, Weintraub D, Elm J, Goudreau JL, Morgan JC, Fang JY, Aminoff MJ, Christine CW, Dhall R, Umeh CC, Boyd JT, Stover N, Leehey M, Zweig RM, Nicholas AP, Bodis-Wollner I, Willis A, Kieburz K, Tilley BC. Longer duration of MAO B inhibitor exposure is associated with clinical decline in Parkinson’s disease. J Park Dis. 2017;7:117–27.

    CAS  Google Scholar 

  • Hirsch EC, Brandel JP, Galle P, Javoy-Agid F, Agid Y. Iron and aluminum increase in the substantia nigra of patients with Parkinson’s disease: an X-ray microanalysis. J Neurochem. 1991;56:446–51.

    Article  CAS  PubMed  Google Scholar 

  • Hirsch EC, Vyas S, Hunot S. Neuroinflammation in Parkinson’s disease. Parkinsonism Relat Disord. 2012;18:S210–2.

    Article  PubMed  Google Scholar 

  • Imamura K, Nishikawa N, Sawada M, Nagatsu T, Yoshida M, Hashizume Y. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 2003;106:518–26.

    Article  CAS  PubMed  Google Scholar 

  • Imamura K, Nishikawa N, Ono K, Suzuki H, Sawada M, Nagatsu T, Yoshida M, Hashizume Y. Cytokine production of activated microglia and decrease in neurotrophic factors of neurons in the hippocampus of Lewy body disease brains. Acta Neuropathol. 2005;109:141–50.

    Article  CAS  PubMed  Google Scholar 

  • Ives NJ, Stowe RL, Marro J, Counsell C, Macleod A, Clarke CE, Gray R, Wheatley K. Monoamine oxidase type B inhibitors in early Parkinson’s disease: meta-analysis of 17 randomized trials involving 3525 patients. Brit Med J. 2004;329:593–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jellinger K, Kienzl E, Rumpelmair G, Riederer P, Stachelberger H, Ben-Shachar D, Youdim MBH. Iron-melanin complex in substantia nigra of parkinsonian brains: an X-ray microanalysis. J Neurochem. 1992;59:1168–71.

    Article  CAS  PubMed  Google Scholar 

  • Jiang H, Wang J, Rogers J, Xie J. Brain iron metabolism dysfunction in Parkinson’s disease. Mol Neurobiol. 2017;54:3078–101.

    Article  CAS  PubMed  Google Scholar 

  • Kim T-I, Mao X, Park H, Chou S-C, Karuppagounder SS, Umanah GE, Yun SP, Brahmachari S, Panicker N, Chen R, Andrabi SA, Qi C, Poirier GG, Pletnikova O, Troncoso JC, Bekris LM, Leverenz JB, Pantelyat A, Ko HS, Rosenthal LS, Dawson TM, Dawson VL. Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson’s disease. Science. 2018;362:557.

    Google Scholar 

  • Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutation in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392:605–8.

    Article  CAS  PubMed  Google Scholar 

  • Kotake Y, Tasaki Y, Hirobe M, Ohta S. Deprenyl decreases an endogenous parkinsonism-inducing compound, 1-benzyl-1,2,3,4-tetrahydroisoquinoline, in mice: in vivo and in vitro studies. Brain Res. 1998;787:341–3.

    Article  CAS  PubMed  Google Scholar 

  • Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic parkinsonism in humans due to a product of meperidine-analog synthesis. Science. 1983;219:979–80.

    Article  CAS  PubMed  Google Scholar 

  • Larsen JP, Boas J, Erdal JK. The Norwegian-Danish study group. Does selegiline modify the progression of early Parkinson’s disease? Results from a five-year study. Eur J Neurol. 1999;6:539–47.

    Article  CAS  PubMed  Google Scholar 

  • Le W. Role of iron in UPS impairment model of Parkinson’s disease. Parkinsonism Relat Disord. 2014;20(Suppl 1):S158–61.

    Article  PubMed  Google Scholar 

  • Liu G, Yu J, Ding J, Xie C, Sun L, Rudenko I, Zheng W, Sastry N, Luo J, Rudow G, Troncoso JC, Cai H. Aldehyde dehydrogenase 1 defines and protects a nigrostriatal dopaminergic neuron subpopulation. J Clin Invest. 2014;124:3032–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lloyd KG, Davidson L, Hornykiewicz O. The neurochemistry of Parkinson’s disease: effect of L-DOPA therapy. J Pharmacol Exp Therap. 1975;153:453–64.

    Google Scholar 

  • Mallajosyula JK, Kaur D, Chinta SJ, Rajagopalan S, Rane A, Nicholls DG, Di Monte DA, Macarthur H, Andersen JK. MAO B elevation in mouse brain astrocytes results in Parkinson’s pathology. PLoS One. 2008;3:e1616.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Maruyama W, Takahashi T, Naoi M. (-)-Deprenyl protects human dopaminergic neuroblastoma SH-SY5Y cells from apoptosis induced by peroxynitrate. J Neurochem. 1998;70:2510–5.

    Article  CAS  PubMed  Google Scholar 

  • Matsubara K. N-methyl-beta-carbonium neurotoxins in Parkinson’s disease. In: Storch A, Collins MA, editors. Neurotoxic factors in Parkinson’s disease and related disorders. New York: Kluwer Academic Publishing/Plenum; 2000. p. 115–30.

    Google Scholar 

  • McGeer EG, McGeer PL. The role of anti-inflammatory agents in Parkinson’s disease. CNS Drugs. 2007;20:351–7.

    Google Scholar 

  • McGeer PL, Itagaki S, Boyes BE, McGeer EG. Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s disease and Alzheimer’s disease brain. Neurology. 1988;38:1285–91.

    Article  CAS  PubMed  Google Scholar 

  • Michel PP, Hirsch EC, Hunot S. Understanding dopaminergic cell death pathways in Parkinson disease. Neuron. 2016;90:678–91.

    Article  CAS  Google Scholar 

  • Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, Oya H, Ozawa T, Kagawa Y. Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochem Biophys Res Commun. 1989;163:1450–5.

    Article  CAS  PubMed  Google Scholar 

  • Mizuno Y, Kondo T, Kuno S, Nomoto M, Yanagisawa N. Early addition of selegiline to L-DOPA treatment is beneficial for patients with Parkinson disease. Clin Neuropharmacol. 2010;33:1–3.

    Article  CAS  PubMed  Google Scholar 

  • Mizuta I, Ohta M, Ohta K, Nishimura M, Mizuta E, Hayashi K, Kuno S. Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes. Biochem Biophys Res Commun. 2000;279:751–5.

    Article  CAS  PubMed  Google Scholar 

  • Mogi M, Harada M, Riederer P, Narabayashi H, Fujita K, Nagatsu T. Tumor necrosis factor-alpha (TNF-alpha) increases in the brain and in the cerebrospinal fluid from parkinsonian patients. Neurosci Lett. 1994a;165:208–10.

    Article  CAS  PubMed  Google Scholar 

  • Mogi M, Harada M, Kondo T, Riederer P, Inagaki H, Minami M, Nagatsu T. Interleukin-1beta, interleukin-6, epidermal growth factor and transforming growth factor-alpha are elevated in the brain from parkinsonian patients. Neurosci Lett. 1994b;180:147–50.

    Article  CAS  PubMed  Google Scholar 

  • Mogi M, Togari A, Kondo T, Mizuno Y, Komure O, Kuno S, Ichinose H, Nagatsu T. Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson’s disease. Neurosci Lett. 1999;270:45–8.

    Article  CAS  PubMed  Google Scholar 

  • Müller T, Riederer P, Grünblatt E. Simultaneous determination of MAO-A and -B activity following first time intake of an irreversible MAO-B inhibitor in patients with Parkinson’s disease. J Neural Transm. 2017;124:745–8.

    Article  PubMed  CAS  Google Scholar 

  • Myllylä VV, Sotaniemi KA, Hakulinen P, Mäki-Ikola O, Heinonen EH. Selegiline as the primary treatment of Parkinson’s disease – a long-term double blind study. Acta Neurol Scand. 1997;95:211–8.

    Article  PubMed  Google Scholar 

  • Mytilineou C, Leonardi EK, Radcliffe P, Heinonen EH, Han S, Werner P, Cohen G, Olanow W. Deprenyl and desmethylselegiline protect mesencephalic neurons from toxicity induced by glutathione depletion. J Pharmacol Exp Therap. 1998;284:700–6.

    CAS  Google Scholar 

  • Nagatsu T. Amine-related neurotoxins in Parkinson’s disease: past, present, and future. Neurotoxicol Teratol. 2002;24:565–9.

    Article  CAS  PubMed  Google Scholar 

  • Nagatsu T, Nagatsu I. Tyrosine hydroxylase (TH), its cofactor tetrahydrobiopterin (BH4), other catecholamine-related enzymes, and their human genes in relation to the drug and gene therapies of Parkinson’s disease (PD): historical overview and future prospects. J Neural Transm. 2016;123:1255–78.

    Article  CAS  PubMed  Google Scholar 

  • Nagatsu T, Sawada M. Inflammatory process in Parkinson’s disease: role for cytokines. Curr Pharm Des. 2005;11:999–1016.

    Article  CAS  PubMed  Google Scholar 

  • Nagatsu T, Sawada M. Molecular mechanism of the relation of monoamine oxidase B and its inhibitors to Parkinson’s disease: possible implication of glial cells. J Neural Transm. 2006a;Suppl 71:53–65.

    Google Scholar 

  • Nagatsu T, Sawada M. Cellular and molecular mechanisms of Parkinson’s disease: neurotoxins, causative genes, and inflammatory cytokines. Cell Mol Neurobiol. 2006b;26:781–802.

    Article  CAS  PubMed  Google Scholar 

  • Nagatsu T, Kato T, Numata Y, Ikuta K, Sano M, Nagatsu I, Kondo Y, Inagaki S, Iizuka R, Hori A, Narabayashi H. Phenylethanolamine N-methyltransferase activity and other enzymes of catecholamine metabolism in human brain. Clin Chim Acta. 1977;75:221–31.

    Article  CAS  PubMed  Google Scholar 

  • Nagatsu T, Mogi M, Ichinose H, Togari A. Cytokines in Parkinson’s disease. J Neural Trnasm. 2000;Suppl 58:143–51.

    Google Scholar 

  • Nakao K, Nakamura C, Sato H, Imamura K, Takeshima T, Nakashima K. Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins. Biochem Biophys Res Commun. 2006;339:915–22.

    Article  CAS  Google Scholar 

  • Naoi M, Maruyama Y, Dostert P, Hashizume Y, Nakahara D, Takahashi T, Ota M. Dopamine-derived endogenous 1(R), 2 (N)-dimethyl-1,2,3,4-tetrahydroisoquinoline, N-methyl-(R)-salsolinol, induced parkinsonism in rats: biochemical, pathological and behavioral studies. Brain Res. 1996;709:285–95.

    Article  CAS  PubMed  Google Scholar 

  • 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.

    Article  CAS  PubMed  Google Scholar 

  • Ozaki N, Nakahara D, Mogi M, Harada M, Kiuchi K, Kaneda N, Miura Y, Kasahara Y, Nagatsu T. Inactivation of tyrosine hydroxylase in rat striatum by 1-methyl-4-phenylpyridinium iron (MPP+). Neurosci Lett. 1988;85:228–32.

    Article  CAS  PubMed  Google Scholar 

  • Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, de Munain AL, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB. Cloning of the gene containing mutations that cause PARK8-linked Parkinson’s disease. Neuron. 2004;44:595–600.

    Article  CAS  PubMed  Google Scholar 

  • Pålhagen S, Heinonen E, Hägglund J, Kaugesaar T, Mäki-Ikola O, Palm R. The Swedish Parkinson study group. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology. 2006;66:1200–6.

    Article  PubMed  Google Scholar 

  • Parkinson Study Group. Effect of tocopherol and deprenyl on the progression of disability in early Parkinson’s disease. N Engl J Med. 1993;328:176–83.

    Article  Google Scholar 

  • PD Med Collaborative Group, Gray R, Ives N, Rick C, Patel S, Gray A, Jenkinson C, McIntosh E, Wheatley K, Williams A, Clarke CE. Long-term effectiveness of dopamine agonists and monoamine oxidase B inhibitors compared with levodopa as initial treatment for Parkinson’s disease (PD MED): a large, open-label, pragmatic randomised trial. Lancet. 2014;384: 1196–205.

    Article  CAS  Google Scholar 

  • Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Deheijia A, Dutra A, Pike B, Root H, Robenstein J, Boyer R, Stenrous ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoiosin RC, DiIorio G, Golbe LI, Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science. 1997;276:2045–7.

    Article  CAS  PubMed  Google Scholar 

  • Przuntek H, Conrad B, Dichgans J, Kraus PH, Krauseneck P, Pergande G, Rinne U, Schimrigk K, Schnitker J, Vogel HP. SELEDO: a 5-year long-term trial on the effect of selegiline in early parkinsonian patients treated with levodopa. Eur J Neurol. 1999;6:141–50.

    Article  CAS  PubMed  Google Scholar 

  • Riederer P. MAO inhibitors and selegiline. In: Nagatsu T, Takahashi A, Yanagisawa N, Mizuno Y, Kondo T, Takahashi R, Mezaki T, Riederer P, Riederer C, editors. From east to west: pioneers in Parkinson’s disease in Japan. Tokyo: QOL Laboratory Corp; 2014. p. 36–7.

    Google Scholar 

  • Riederer P, Berg D, Casadei N, Cheng F, Classen J, Dresel C, Jost W, Krüger R, Müller T, Reichmann H, Rieß O, Storch A, Strobel S, van Eimeren T, Völker HU, Winkler J, Winklhofer KF, Wüllner U, Zunke F, Monoranu CM. alpha-Synuclein in Parkinson's disease: causal or bystander? J Neural Transm. 2019;126:815–840.

    Google Scholar 

  • Robakis D, Fahn S. Defining the role of the monoamine oxidase-B inhibitors for Parkinson’s disease. CNS Drugs. 2015;29:433–41.

    Article  CAS  PubMed  Google Scholar 

  • Sánchez-Danés A, Richaud-Patin Y, Carballo-Carbajal I, Jiménez-Delgado S, Caig C, Mora S, Di Guglielmo C, Ezglielmo C, Ezguerra M, Patel B, Gilalt A, Canals JM, Memo M, Auberch J, López-Barneo J, Vila M, Cuervo AM, Tolsa E, Consiglic A, Raya A. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson’s disease. EMBO Mol Med. 2012;4:380–95.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Schapira AHV, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD. Mitochondrial complex I deficiency in Parkinson’s disease. Lancet. 1989;1:1269.

    Article  CAS  PubMed  Google Scholar 

  • Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Imai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000;25:302–5.

    Article  CAS  PubMed  Google Scholar 

  • Shoulson I, Oakes D, Fahn S, Lang A, Langston JW, LeWitt P, Olanow CW, Penney JB, Tanner C, Kieburtz K, Rudolph A, the Parkinson Study Group. Impact of sustained deprenyl (selegiline) in levodopa-treated Parkinson’s disease: a randomized placebo-controlled extension of the deprenyl and tocopherol antioxidative therapy of Parkinsonism trial. Ann Neurol. 2002;51:604–12.

    Article  CAS  PubMed  Google Scholar 

  • Singh N, Haldar S, Tripathi AK, McElwee KK, Horback K, Beserra A. Iron in neurodegenerative disorders of protein misfolding: a case of prion disorders and Parkinson’s. Antioxid Redox Signal. 2014;21:471–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sofic E, Riederer P, Heisen H, Bechmann H, Reynolds GP, Hebenstreit G, Youdim MBH. Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm. 1988;74:199–205.

    Article  CAS  PubMed  Google Scholar 

  • Tang YP, Ma YL, Chao CC, Chen KY, Lee EHI. Enhanced glial cell line-derived neurotrophic factor mRNA expression upon (-)-deprenyl and melatonin treatments. J Neurosci Res. 1998;53:593–604.

    Article  CAS  PubMed  Google Scholar 

  • Tatton WG, Wadia JS, Ju WYH, Chalmers-Redman RMA, Tatton NA. (-)-Deprenyl reduces neuronal apoptosis and facilitates neuronal outgrowth by altering protein synthesis without inhibiting monoamine oxidase. J Neural Trnsm. 1996;48:45–59.

    CAS  Google Scholar 

  • Tetrud JW, Langston JW. The effect of deprenyl (selegiline) on the natural history of Parkinson’s disease. Science. 1989;245:519–22.

    Article  CAS  PubMed  Google Scholar 

  • Valente EM, Abou-Sleiman PM, Caputo V, Muqit MMK, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304:1158–60.

    Article  CAS  PubMed  Google Scholar 

  • Woodard CM, Campos BA, Kuo S-H, Nirenberg MJ, Nestor MW, Zimmer M, Mosharov E, Sulzer D, Zhou H, Paul D, Clark L, Schadt EE, Sardi SP, Rubin L, Eggan K, Brock M, Lipnick S, Rao M, Chang S, Li S, Noggle S. iPS cell derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson’s disease. Cell Rep. 2014;9:1173–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Youdim MB, Fridkin M, Zheng H. Bifunctional drug derivatives of MAO B inhibitor rasagiline and iron chelator VK-28 rasagiline as a more effective approach to treatment of brain aging and aging neurodegenerative diseases. Mech Aging Dev. 2005;126:317–26.

    Article  CAS  PubMed  Google Scholar 

  • Zhao YJ, Wee HL, Au WL, Seah SH, Luo N, Li SC, Tan LCS. Selegiline use is associated with a slower progression in early Parkinson’s disease as evaluated by Hoehn and Yahr stage transition times. Parkinsonism Relat Disord. 2011;17:194–7.

    Article  CAS  PubMed  Google Scholar 

  • Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessel AJ, Pfeiffer RF, Patenge N, Carbajal IC, Viergge P, Asmus F, Mueller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004;44:601–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Research Promotion and Support, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  2. Department of Physiological Chemistry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Akira Nakashima

Authors
  1. Toshiharu Nagatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akira Nakashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toshiharu Nagatsu .

Editor information

Editors and Affiliations

  1. Dept Psychiatry , Psychosomatics & Psychotherapy, University of Würzburg, Medical School Clinical Neurochemistry, Würzburg, Germany

    Peter Riederer

  2. Inst für Psychologische Medizin, Haag, Bayern, Germany

    Gerd Laux

  3. Department of Psychiatry, University of Toronto Department of Psychiatry, Toronto, ON, Canada

    Benoit Mulsant

  4. Center Translational Res Neurol Diseases, Dalian Med Uni Shanghai Inst Health Sc Center Translational Res Neurol Diseases, Dalian, China

    Weidong Le

  5. Fujita Health University School Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

Section Editor information

  1. Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Toshiharu Nagatsu

  2. Department of Physiological Chemistry, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Akira Nakashima

Rights and permissions

Reprints and permissions

Copyright information

© 2020 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Nagatsu, T., Nakashima, A. (2020). Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson’s Disease. In: Riederer, P., Laux, G., Mulsant, B., Le, W., Nagatsu, T. (eds) NeuroPsychopharmacotherapy. Springer, Cham. https://doi.org/10.1007/978-3-319-56015-1_238-2

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-56015-1_238-2

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-56015-1

  • Online ISBN: 978-3-319-56015-1

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson’s Disease
    Published:
    10 April 2020

    DOI: https://doi.org/10.1007/978-3-319-56015-1_238-2

  2. Original

    Monoamine Oxidase Inhibitor (MAO-I)-Mediated Neuroprotection for Treating Parkinson’s Disease
    Published:
    19 November 2019

    DOI: https://doi.org/10.1007/978-3-319-56015-1_238-1

Search

Navigation