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Review

Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson’s disease

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Pages 1233-1250 | Published online: 09 Jan 2014

References

  • Dauer W, Przedborski S. Parkinson’s disease: mechanisms and models. Neuron39(6), 889–909 (2003).
  • Eriksen JL, Wszolek Z, Petrucelli L. Molecular pathogenesis of Parkinson’s disease. Arch. Neurol.62(3), 353–357 (2005).
  • Dandhi S, Wood NW. Molecular pathogenesis of Parkinson’s disease. Hum. Mol. Genet.14(18), 2749–2755 (2005).
  • Savitt JM, Dawson VL, Dawson TM. Diagnosis and treatment of Parkinson’s disease: molecules to medicine. J. Clin. Inv.116(7), 1744–1754 (2006).
  • Thomas B, Beal MF. Parkinson’s disease. Human Mol. Genet.16(Spec. No.2), R183–R194 (2007).
  • Vila M, Przedborski S. Genetic clues to the pathogenesis of Parkinson’s disease. Nat. Med.10(Suppl.), S58–S62 (2004)
  • Sun F, Kanthasamy A, Anantharam V, Kanthasamy AG. Environmental neurotoxic chemicals-induced ubiquitin proteasome system dysfunction in the pathogenesis and progression of Parkinson’s disease. Pharmacol. Ther.114(3), 327–344 (2007).
  • Bogaerts V, Theuns J, van Broeckhoven C. Genetic findings in Parkinson’s disease and translation into treatment: a leading role for mitochondria? Genes Brain Behav.7(2), 129–151 (2008).
  • Terzioglu M, Galter D. Parkinson’s disease: genetic versus toxin-induced rodent models. FEBS J.275(7), 1384–1391 (2008).
  • Ethell DW, Fei Q. Parkinson-linked genes and toxins that affect neuronal cell death through the Bcl-2 family. Antiox. Redox Signal.11(3), 1–12 (2009).
  • Tatton WG, Chalmers-Redman R, Brown D, Tatton N. Apoptosis in Parkinson’s disease: signals for neural degradation. Ann. Neurol.53(Suppl.), S61–S72 (2003).
  • Esposito E, Matteo VD, Giovanni GD. Death in the substantia nigra: a motor tragedy. Expert Rev. Neurother.7(6), 677–697 (2007).
  • Dick FD, De Palma G, Almadi A et al. Environmental risk factors for Parkinson’s disease and parkinsonism: the Geoparkinson study. Occup. Environ. Med.64(10), 666–672 (2007).
  • Bonsi P, Cuomo D, Martella G et al Mitochondrial toxins in basal ganglia disorders: from animal models to therapeutic strategies. Curr. Neuropharmacol.4(1), 69–75 (2006).
  • Naoi M, Maruyama W, Nagy GM. Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brain. Neuro. Toxicol.25(1–2), 193–204 (2004).
  • Abou-Sleiman PM, Muqit MMK, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson’s disease. Nat. Rev. Neurosci.7(3), 207–219 (2006).
  • Lesage S, Brice A. Parkinson’s disease: from monogenic forms to genetic susceptibility factors. Hum. Mol. Genet.18(R1), R48–R59 (2009).
  • Waldmeier PC, Tatton WG. Interrupting apoptosis in neurodegenerative disease: potential for effective therapy? Drug Discov. Today9(5), 210–218 (2004).
  • Sulzer D. Multiple hit hypotheses for dopamine neuron loss in Parkinson’s disease. Trends Neurosci.30(5), 244–250 (2007).
  • Fischer U, Sculze-Osthoff K. New approaches and therapeutic targeting apoptosis in disease. Pharmacol. Rev.57(2), 187–215 (2005).
  • Green DR, Kroemer G. Pharmacological manipulation of cell death: clinical applications in sight? J. Clin. Invest.115(10), 2610–2617 (2005).
  • Braak H, Tredici KD, Rüb U, de Vos RAL, Jansen Steur ENH, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol. Aging24(2), 197–211 (2003).
  • Braak H, Ghebremedhin E, Rüb U, Bratzke H, Tredici KD. Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res.318(1), 121–134 (2004).
  • Török TL, Klebovich I. Monoamine Oxidase Inhibitors and Their Role in Neurotransmission (Drug Development). Medicina Publishing House (Eds). Budapest, Hungary 1–403 (2004).
  • Schapira AHV, Olanow AW. Neuroprotection in Parkinson disease: mysteries, myths, and misconceptions. JAMA291(3), 358–364 (2004).
  • Jenner P. Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson’s disease. Neurology63(Suppl. 2), S13–S31 (2004).
  • Schapira AH, Bezard E, Brotchie J et al. Novel pharmacological targets for the treatment of Parkinson’s disease. Nat. Rev. Drug Discov.5(10), 845–854 (2006).
  • Elmer LW, Bertoni JM. The increasing role of monoamine oxidase type B inhibitors in Parkinson’s disease therapy. Expert Opin. Pharmacother.9(16), 2759–2772 (2008).
  • Edmondson DE, Mattevi A, Binda C, Li M, Hubalek F. Structure and mechanism of monoamine oxidase. Cur. Med. Chem.11(15), 1983–1993 (2004).
  • Edmondson DE, Binda C, Mattevi A. Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B. Arch. Biochem. Biophys.464(2), 269–276 (2007).
  • Shih JC. Monoamine oxidases: from tissue homogenates to transgenic mice. Neurochem. Res.32(10), 1757–1761 (2007).
  • Kumar MJ, Anderson JK. Perspectives on MAO-B in aging and neurological disease. Mol. Neurobiol.30(1), 77–89 (2004).
  • Parsian A, Racette B, Zhang ZH, Rundle M, Perlmutter JS. Association of variations in monoamine oxidases A and B with Parkinson’s disease subgroups. Genomics83(3), 454–460 (2004).
  • Cordata DJ, Chan DKY. Genetics and Parkinson’s disease J. Clin. Neurosci.11(2), 119–123 (2004).
  • Bialecka M, Klodowska-Duda G, Honczarenko K et al. Polymorphisms of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAOB), N-acetyltransferase 2 (NAT2), and cytochrome P450 2D6 (CYP2D6) gene in patients with early onset of Parkinson’s disease. Parkinsonism Relat. Disord.13(4), 224–229 (2007).
  • Singh M, Khan AJ, Shah PP, Shukla R, Khanna VK, Parmar D. Polymorphism in environment responsive genes and association with Parkinson disease. Mol. Cell Biochem.312(1–2), 131–138 (2008).
  • Gao X, Scott WK, Wang G et al. Gene–gene interaction between FGF20 and MAOB in Parkinson disease. Ann. Human Genet.72(Pt 2), 157–162 (2008).
  • Alia-Klein N, Goldstein RZ, Kriplani A et al. Brain monoamine oxidase A activity predicts trait aggression. J. Neurosci.28(19), 5099–5104 (2008).
  • Wu YH, Fisher DF, Swaab DF. A promotor polymorphism in the monoamine oxidase A gene is associated with the pineal MAOA activity in Alzheimer’s disease patients. Brain Res.116, 13–19 (2007).
  • Yu YW, Tsai SJ, Hong CJ, Chen TJ, Chen MC, Yang CW. Association study of a monoamine oxidase: a gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropharmacology39(9), 1719–1723 (2005).
  • Cohen IL, Liu X, Schutz C et al. Association of autism severity with a monoamine oxidase: a functional polymorphism. Clin. Genetics64(3), 190–197 (2003).
  • Riederer P, Lachenmayer L, Laux G. Clinical applications of MAO-inhibitors. Curr. Med. Chem.11(13), 2033–2043 (2004).
  • Youdim MBH, Edmondson D, Tipton KF. The therapeutic potential of monoamine oxidase inhibitors. Nat. Rev. Neurosci.7(4), 295–309 (2006).
  • Youdim MBH, Bakhle YS. Monoamine oxidase: isoforms and inhibitors in Parkinson’s disease and depressive illness. Br. J. Pharmacol.147(Suppl. 1), S287–S296 (2006).
  • Binda C, Li M, Hubalek F, Reselli N, Edmondson DE, Mattevi A. Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structure. Proc. Natl Acad. Sci. USA100(17), 9750–9755 (2003).
  • Binda C, Hubalek F, Li M et al. Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J. Med. Chem.47(7), 1360–1366 (2004).
  • Binda C, Hubalek F, Castagnoli N, Edmondson DE, Mattevi A. Structure of the human mitochondrial monoamine oxidase B: new chemical implications for neuroprotective drug design. Neurology67(Suppl. 2), S5–S7 (2006).
  • Hualek F, Binda C, Khalil A, Mattevi A, Catagnoli N, Edmondson DE. Demonstration of isoleucine 199 as a structural determination for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors. J. Biol. Chem.280(22), 15761–15766 (2005).
  • De Colibus L, Li M, Binda C, Lustig A, Edmondson DE, Mattevi A. Three-dimensional structure of human monoamine oxidase (MAO A): relation to the structures of rat MAO A and human MAO B. Proc. Natl Acad. Sci. USA102(36), 12684–12689 (2005).
  • Son S, Ma J, Kondou Y, Yoshimura M, Yamashita E, Tsukihara T. Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors. Proc. Natl Acad. Sci. USA105(15), 5739–5744 (2008).
  • Magyar K, Palfi M, Tabi T, Kalasz H, Szende B, Szoko E. Pharmacological aspects of (-)-deprenyl. Curr. Med. Chem.11(15), 2017–2031 (2004).
  • Muralikrishnan D, Samantary S, Mohamalumar KP. D-deprenyl protects nigro–striatal neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity. Synapse50(1), 7–13 (2003).
  • Ebadi M, Brown-Borg H, Ren J et al. Therapeutic efficacy of selegiline in neurodegenerative disorders and neurological diseases. Curr. Drug Targets7(11), 1513–1529 (2006).
  • Riederer P, Lachenmayer L. Selegiline’s neuroprotective capacity revisited. J. Neural Transm.110(11), 1273–1278 (2003).
  • Palhagen S, Heinonen E, Hagglund J, Kaugesaar T, Maki-Ikoda O, Palm R; Swedish Parkinson Study Group. Selegiline slows the progression of the symptoms of Parkinson disease. Neurology66(8), 1200–1206 (2006).
  • Lev N, Melamed E, Offen D. Apoptosis and Parkinson’s disease. Prog. Neuropsycopharmacol. Biol. Psychiat.27(2), 245–250 (2003).
  • Malagelada C, Ryu EJ, Biswas SC, Jackson-Lewis V, Green LA. RTP801 is elevated in parkinsonian brain substantia nigral neurons and mediates death in cellular models of Parkinson’s disease by a mechanism involving mammalian target of rapamycin inactivation. J. Neurosci.26(49), 9996–10005 (2006).
  • Mogi M, Kondo T, Mizuno Y, Nagatsu T. p53 protein, interferon-g, and NF-κB levels are elevated in the parkinsonian brain. Neurosci. Lett.414(1), 94–97 (2007).
  • Nagatsu T, Sawada M. Biochemistry of postmortem brains in Parkinson’s disease: historical overview and future prospects. J. Neural Transm. Suppl.72, 113–120 (2007).
  • Betartbet B, Anderson LR, Gearing M et al. Fas-associated factor 1 and Parkinson’s disease. Neurobiol. Dis.31(3), 309–315 (2008).
  • Naoi M, Maruyama W, Akao Y, Yi H. Mitochondria determine the survival and death in apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, and neuroprotection by propargylamines. J. Neural Transm.109(5–6), 607–621 (2002).
  • Akao Y, Maruyama W, Shimizu S et al. Mitochondrial permeability transition mediates apoptosis induced by N-methyl(R)salsolinol, an endogenous neurotoxin, and its inhibited by Bcl-2 and rasagiline, N-propargyl-1(R)-aminoindan. J. Neurochem.82(4), 913–923 (2002).
  • Novikova L, Garris BL, Garris DR, Lau YS. Early signs of neuronal apoptosis in the substantia nigra pars compacta of the progressive neurodegenerative mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pribenecid model of Parkinson’s disease. Neuroscience14(1), 67–76 (2006).
  • Chin MH, Oian WJ, Wang H et al. Mitochondrial dysfunction, oxidative stress, and apoptosis revealed by proteomic and transcriptomic analyses of the striatum in two mouse models of Parkinson’s disease. J. Proteome Res.7(2), 666–677 (2008).
  • Naoi M, Maruyama W, Yi H et al. Neuromelanin selectively induces apoptosis in dopaminergic SH-SY5Y cells by deglutathionylation in mitochondria: involvement of the protein and melanin component. J. Neurochem.105(6), 2489–2500 (2008).
  • Kinnally KW, Antinsson B. A tale of two mitochondrial channels, MAC and PTP, in apoptosis. Apoptosis12(5), 857–868 (2007)
  • Kroemer G, Galluzzi L, Brenner C. Mitochondrial membrane permeabilization in cell death. Physiol. Rev.87(1), 99–163 (2007).
  • Tsujimoto Y, Shimizu S. Role of the mitochondrial membrane permeability transition in cell death. Apoptosis12(5), 835–840 (2007).
  • Maruyama W, Akao Y, Youdim MB, Davis BA, Naoi M. Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous neurotoxin, N-methyl(R)salsolinol. J. Neurochem.78(4), 727–735 (2001).
  • Soane L, Fiskum G. TAT-mediated endocytotic delivery of the loop deletion Bcl-2 protein protects neurons against cell death. J. Neurochem.95(1), 230–243 (2005).
  • Lin CF, Chen CL, Chang WT et al. Bcl-2 rescues ceramide- and etoposide-induced mitochondrial apoptosis through blockage of caspase-2 activation. J. Biol. Chem.280(25), 23758–23765 (2005).
  • Malok JMI, Shevtsova Z, Bähr M, Kuugler S. Long-term in vivo inhibition of CNS neurodegeneration by Bcl-XL gene transfer. Mol. Ther.11(3), 373–381 (2005).
  • Letal A. Pharmacological manipulation of Bcl-2 family members to control cell death. J. Clin. Invest.115(10), 2648–2655 (2005).
  • Shacka JJ, Roth KA. Regulation of neuronal cell death and neurodegeneration by members of Bcl-2 family: therapeutic implications. Curr. Drug Targets CNS Neurol. Disord.4(1), 25–39 (2005).
  • Soane L, Fiskum G. Inhibition of mitochondrial neural cell death pathways by protein transduction of Bcl-2 family proteins. J. Bioenerg. Biomembr.37(3), 179–190 (2005).
  • Shacka JJ, Roth KA. Bcl-2 family and the central nervous system: from rheostat to real complex. Cell Death Differ.13(8), 1299–1304 (2006).
  • Liu B. RNA interference technologies for understanding and treating neurodegenerative diseases. NeuroMolecular Med.6(1), 1–12 (2004).
  • Ralph GS, Mazarakis ND. Therapeutic gene silencing in neurological disorders, using interfering RNA. J. Mol. Med.83(6), 413–419 (2005).
  • Manfredsson EP, Lewin AS, Mandel RJ. RNA knockdown as a potential therapeutic strategy in Parkinson’s disease. Gene Ther.13(6), 517–524 (2006).
  • Akao Y, Maruyama W, Yi H, Shamoto-Nagai M, Youdim MB, Naoi M. An anti-Parkinson’s disease drug, N-propargyl-1(R)-aminoindan (rasagiline) enhances expression of antiapoptotic bcl-2 in human dopaminergic SH-SY5Y cells. Neurosci. Lett.326(2), 105–108 (2002).
  • Maruyama W, Takahashi T, Youdim M, Naoi M. The anti-Parkinson drug, rasagiline, prevents apoptotic DNA damage induced by peroxynitrite in human dopaminergic neuroblastoma SH-SY5Y cells. J. Neural Transm.109(4), 467–481 (2002).
  • Maruyama W, Akao Y, Carrillo MC, Kitani K, Youdim MBH, Naoi M. Neuroprotection by propargylamines in Parkinson’s disease. Suppression of apoptosis and induction of prosurvival genes. Neurotoxicol. Teratol.24(5), 675–682 (2002).
  • Maruyama W, Yi H, Takahashi T et al Neuroprotective function of R-(-)-1-(benzofuran-2-yl)-2-propargylaminopentane, [R-(-)-BFAP] against apoptosis induced by N-methyl(R)salsolinol, an endogenous dopaminergic neurotoxin, in human dopaminergic neuroblastoma SH-SY5Y cells. Life Sci.75(1), 107–117 (2004).
  • Blandini F, Armentero MT, Fancellu R, Blaugrund E, Nappi G. Neuroprotective effect of rasagiline in a rodent model of Parkinson’ disease. Exp. Neurol.187(2), 455–459 (2004).
  • Yi H, Maruyama W, Akao Y et al.N-Propargylamine protects SH-SY5Y cells from apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, through stabilization of mitochondrial membrane and induction of anti-apoptotic Bcl-2. J. Neural Transm.113(1), 21–32 (2006).
  • Naoi M, Maruyama W, Akao Y, Yi H, Yamaoka T. Involvement of type A monoamine oxidase in neurodegeneration: regulation of mitochondrial signaling leading cell death or neuroprotection. J. Neural Transm. Suppl.71, 67–77 (2006).
  • Naoi M, Maruyama W, Yi H, Akao Y, Yamaoka Y, Shamoto-Nagai M. Neuroprotection by propargylamines in Parkinson’s disease: intracellular mechanism underlying the anti-apoptotic function and search for clinical markers. J. Neural Transm. Suppl.72, 121–131 (2007).
  • Mandel SA, Sagi Y, Amit T. Rasagiline promotes regeneration of substantia nigra dopaminergic neurons in post-MPTP-induced Parkinsonism via activation of tyrosine kinase receptor signaling pathway. Neurosci. Res.32(10), 1694–1699 (2007).
  • Bar-Am O, Amit T, Youdim MB. Aminoindan and hydroxyaminoindan metabolites of rasagiline and ladostigil, respectively, exert neuroprotective properties in vitro. J. Neurochem.104(2), 500–508 (2007).
  • Speiser Z, Mayk A, Litinetsky Let al. Rasagiline is neuroprotective in an experimental model of brain ischemia in the rat. J. Neural Transm.114(5), 595–605 (2007).
  • Zhu W, Xie W, Pan Tet al. Comparison of neuroprotective and neurorestorative capabilities of rasagiline and selegiline against lactacystin-induced nigro–striatal dopamine degeneration. J. Neurochem.105(5), 1970–1978 (2008).
  • Binda C, Hubalek F, Li Met al. Binding of rasagiline-related inhibitors to human monoamine oxidases; a kinetic and crystallographic analysis. J. Med. Chem.48(26), 8148–8154 (2005).
  • Maruyama W, Nitta A, Shamoto-Nagai M, et al.N-Propargyl-1-(R)-aminoindan, rasagiline, increases glial cell line-derived neurotrophic factor (GDNF), in neuroblastoma SH-SY5Y cells through activation of NF-κB transcription factor. Neurochem. Int.44(6), 293–400 (2004).
  • Weireb O, Bar-Am O, Amit T, Chillag-Talmor O, Youdim MBH. Neuroprotection via pro-survival protein kinase C isoforms associated with Bcl-2 family members. FASEB J.18(12), 1471–1473 (2004).
  • Bar-Am O, Weinreb O, Amit T, Youdim MB. Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neurorescue activity of propargylamine. FASEB J.19(13), 1899–1901 (2005).
  • Hirai C, Takahara K, Shimizu Set al. Effects of R-(-)-BPAP on the expression of neurotrophins and their receptors in mesencephalic slices. Biol. Pharm. Bull.28(8), 1524–1526 (2006).
  • Bespalov MB, Saarma M. GDNF family receptor complexes are emerging drug targets. Trends Pharmacol. Sci.28(2), 69–74 (2007).
  • Zheng JS, Tang LL, Zheng SS, Zhan RY et al. Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson’s disease. Brain Res. Mol. Brain Res.134(1), 155–161 (2005).
  • Sun M, Kong L, Wang X, Lu X, Gao Q, Geller AI. Comparison of the capacity of GDNF, BDNF, or both, to protect nigrostrial neurons in a rat model of Parkinson’s disease. Brain Res.1052(2), 119–129 (2005).
  • Do Thi NA, Saillour P, Ferrero L, Paunio T, Mallet J. Does neuronal expression of GDNF effectively protect dopaminergic neurons in a rat model of Parkinson’s disease? Gene Ther.14(5), 441–450 (2007).
  • Gill SS, Patel NK, Hotton GR et al. Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson’s disease. Nat. Med.9(5), 589–595 (2003).
  • Lang AE, Gill S, Pael NK et al. Randomized controlled trial of intraputamenal glial cell-line-derived neurotrophic factor infusion in Parkinson disease. Ann. Neurol.59(3), 459–466 (2006).
  • Slevin JT, Gash DM, Smith CD et al. Unilateral intraputamenal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year of treatment and 1 year of withdrawal. J. Neurosurg.106(4), 614–620 (2007).
  • Dietz GP, Valbuena PC, Dietz B et al. Striatal delivery of neurturin by CERE-120, an AAV2 vector for the treatment of dopaminergic neuron degeneration in Parkinson’s disease. Mol. Ther.15(1), 62–68 (2007).
  • Grondin R, Zhang Z, Ai Yet al. Intraputamenal infusion of exogenous neurturin protein restores motor and dopaminergic function in the globus pallidus of MPTP-lesioned rhesus monkeys. Cell Transplant.17(4), 373–381 (2008).
  • Marks WJ, Ostrem JL, Verhagen L et al. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson’s disease: an open-trial, Phase 1 trial. Lancet Neurol.7(5), 400–408 (2008).
  • Dietz GP, Valbuena PC, Dietz B et al. Application of a blood–brain-barrier-penetrating form of GDNF in a mouse model for Parkinson’s disease. Brain Res.1082(1), 61–66 (2006).
  • Kunikowska G, Gallagher I, Glover V, Clow A, Jenner P. Effects of short- and long-term (-)-deprenyl administration on mRNA for copper, zinc- and manganese-superoxide dismutase and glutathione peroxidase in rat brain. Brain Res.953(1–2), 1–11 (2002).
  • Andoh T, Chock PB, Murphy DL, Chiueh CC. Role of the redox protein thioredoxin in cytoprotective mechanism evoked by (-)-deprenyl. Mol. Pharmacol.68(5), 1408–1414 (2005).
  • Nakaso 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.339(3), 915–922 (2006).
  • Takahata K, Shimizu S, Katsuki H, Yoneda F, Akaike A. Effects of selegiline on antioxidant systems in the nigrostriatum in rat. J. Neural Transm.113(2), 151–158 (2006).
  • Sariola H, Saarma M. Novel functions and signal pathways for GDNF. J. Cell Sci.116(19), 3855–3862 (2003).
  • Almeida RD, Manadas BJ, Melo CV et al. Neuroprotection by BDNF against glutamate-induced apoptotic cell death is mediated by ERK and PI3-kinase pathways. Cell Death Differ.12(10), 1329–1343 (2005).
  • Reichardt LF. Neurotrophin-regulated signaling pathways. Philos. Trans. R. Soc. Lond. B361(1473), 1545–1564 (2006).
  • Yogev-Falach M, Amit T, Bar-Am O, Youdim MBH. The importance of propargylamine moiety in the anti-Parkinson drug rasagiline and its derivatives for MAPK-dependent amyloid precursor protein processing. FASEB J.17(15), 2325–2327 (2003).
  • Bar-Am O, Yogev-Falach M, Amit T, Sagi Y, Youdim MBH. Regulation of protein kinase C by the anti-parkinson drug, MAO-B inhibitor rasagiline and its derivatives, in vivo. J. Neurochem.85(5), 1119–1125 (2004).
  • Karin M, Lin A. NF-κB at the crossroads of life and death. Nat. Immunol.3(3), 221–227 (2002).
  • Camandola S, Mattson MP. NF-κB as a therapeutic target in neurodegeneration. Expert Opin. Ther. Targets11(2), 123–132 (2007).
  • Nifboer CG, Heijnen CJ, Groenendaal F, May MJ, van Bel F, Kavelaars A. A dual role of NF-κB pathway in neonatal-ischemic brain damage. Stroke39(9), 2578–2586 (2008).
  • Soos J, Engelhardt JI, Siklos L, Havas L, Majtenyi K. The expression of PARP, NF-κB and parvalbumin is increased in Parkinson’s disease. Neuroreport15(11), 1715–1718 (2004).
  • Onyango IG, Tuttle JB, Bennett JP Jr. Activation of p38 and n-acetylcysteine-sensitive c-Jun NH2-terminal kinase signaling cascade is required for induction of apoptosis in Parkinson’s disease cybrids. Mol. Cell Neurosci.28(3), 452–461 (2005).
  • Ghosh A, Roy A, Liu X et al. Selective inhibition of NF-κB activation prevents dopaminergic neuronal loss in a mouse model of Parkinson’s disease. Proc. Natl Acad. Sci. USA104(47), 18754–18759 (2007).
  • Fridmacher V, Katschmidt B, Goudeau B et al. Forebrain-specific neuronal inhibition of nuclear factor-κB activity leads to loss of neuroprotection. J. Neurosci.23(28), 9403–9408 (2003).
  • Jang JH, Surh YJ. Bcl-2 attenuation of oxidative cell death is associated with up-regulation of γ-glutamylcysteine ligase via constitutive NF-κB activation. J. Biol. Chem.279(37), 38779–38786 (2004).
  • Rojo AI, Salinas M, Marin D, Perona R, Guadrado A. Regulation of Cu/Zn-superoxide dismutase expression via the phosphatidylinositol 3 kinase/Akt pathway and nuclear factor-κB. J. Neurosci.24(33), 7324–7334 (2004).
  • Hoffmann A, Leung TH, Baltimore S. Genetic analysis of NF-κB/Rel transcription factors defines functional species. EMBO J.22(20), 5530–5539 (2003).
  • Sharma SK, Carlson EC, Ebadi M. Neuroprotective actions of selegiline in inhibiting 1-methyl,4-phenylpyridinium ion (MPP+)-induced apoptosis in SK-N-SH neurons. J. Neurocytol.32(4), 329–343 (2003).
  • Chong ZZ, Meise K. Erythropietin requires NF-κB and its nuclear translocation to prevent early and late apoptotic neural injury during β-amyloid toxicity. Curr. Neurosci. Res.2(5), 387–399 (2005).
  • Henn IG, Bouman L, Schlehe J et al. Parkin mediates neuroprotection through activation of IκB kinase/nuclear factor-κB signaling. J. Neurosci.27(8), 1868–1878 (2007).
  • Maruyama W, Weinstock M, Youdim MBH, Nagai M, Naoi M. Anti-apoptotic action of anti-Alzheimer drug, TV3326 [(N-propargyl)-(3R)- aminoindan-5-yl]-ethyl methyl carbamate, a novel cholinesterase-monoamine oxidase inhibitor. Neurosci. Lett.341(3), 233–236 (2003).
  • Chiou SH, Ku HH, Tsai TH et al. Moclobemide upregulated Bcl-2 expression and induce neural stem cell differentiation into serotoninergic neurons via extracellular-regulated kinase pathway. Br. J. Pharmacol.148(5), 587–598 (2006).
  • Mallajosyula JK, Kauer D, Chinta SJ et al., MAO-B elevation in mouse brain astrocytes results in Parkinson’s pathology. PLoS One3(2), E1616 (2008).
  • Fornsi F, Giogi FS, Gesi M, Chen K, Alessri MG, Shih JC. Biochemical effects of the monoamine neurotoxins DSP-4 and MDMA in specific brain regions of MAO-B-deficient mice. Synapse39(3), 213–221 (2001).
  • Yi H, Akao Y, Maruyama W, Chen K, Shih, Naoi M. Type A monoamine oxidase is the target of an endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, leading to apoptosis in SH-SY5Y cells. J. Neurochem.96(2), 541–549 (2006).
  • Maragos WF, Young KL, Altman CS et al. Striatal damage and oxidative stress induced by the mitochondrial toxin malonate are reduced in clorgyline-treated rats and MAO-A deficient mice. Neurochem. Res.29(4), 741–746 (2004).
  • Fitzgerald JC, Ufer C, De Girolamo LA, Kuhn H, Billet EE. Monoamine oxidase-A modulates apoptotic cell death induced by staurosporine in human neuroblastoma cells. J. Neurochem.103(6), 2189–2199 (2007).
  • Ou XM, Chen K, Shih JC. Monoamine oxidase A and repressor R1 are involved in apoptotic signaling pathway. Proc. Natl Acad. Sci. USA103(29), 10923–10928 (2006).
  • Chen K, Ou XM, Chen G, Choi SH, Shih JC. R1, a novel repressor of the human monoamine oxidase A. J. Biol. Chem.280(12), 11552–11559 (2005).
  • Wong WK, Ou XM, Chen K, Shih JC. Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. J. Biol. Chem.277(25), 22222–22230 (2002).
  • Jiang H, Jiang Q, Liu W, Feng J. Parkin suppresses the expression of monoamine oxidases. J. Biol. Chem.281(13), 8591–8599 (2006).
  • Holt A, Berry MD, Boulton AA. On the binding of monoamine oxidase inhibitors to some sites distinct from the MAO active site, and effects thereby elicited. Neurotoxicology25(1–2), 251–266 (2004).
  • Holt A, Wieland B, Baker GB. Allosteric modulation of semicarbazide-sensitive amine oxidase activities in vitro by imidazoline receptor ligands. Br. J. Pharmacol.143(4), 495–507 (2004).
  • Anderson NJ, Lupo PA, Nutt DJ, Hudson AL, Robinson ESL. Characterisation of imidazoline I2 binding sites in pig brain. Eur. J. Pharmacol.519(1–2), 68–74 (2004).
  • Anderson NJ, Seif I, Nutt DJ, Hudson AL, Robinson ES. Autoradiographical distribution of imidazoline binding sites in monoamine oxidase A deficient mice. J. Neurochem.96(6), 1551–1559 (2006).
  • Hara MR, Thomas B, Cacio MB et al. Neuroprotection by pharmacologic blockade of the GADPH death cascade. Proc. Natl Acad. Sci. USA103(81), 3887–3889 (2006).
  • Hara M, Snyder SH. Nitric oxide-GAPDH-Siah: a novel cell death cascade. Cell Mol. Neurobiol.26(4–6), 527–538 (2006).
  • Levant B, Morgan KA, Ahlgren-Beckendorf JA et al Modulation of [3H]quinopirole binding at striatal D2 dopamine receptor by a monoamine-A-like site: evidence from radioligand studies and D2-receptor- and MAO(A)-deficient mice. Life Sci.70(2), 229–241 (2001).
  • Ohta K, Kuno S, Mizuta I, Fujinami A, Matsui H, Ohta M. Effects of dopamine agonists bromocriptine, pergolide, cabergoline, and SKF-38393 on GDNF, NGF, and BDNF synthesis in cultured mouse astrocytes. Life Sci.73(5), 517–626 (2003).
  • Ohta K, Fujinami A, Kuno S et al. Cabergoline stimulates synthesis and secretion of nerve growth factor, brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor by mouse astrocytes in primary culture. Pharmacology71(3), 162–168 (2004).
  • Jorda EG, Jimenez A, Verdaguer E et al. Evidence in favour of a role for peripheral-type benzodiazepine receptor ligands in amplification of neural apoptosis. Apoptosis10(1), 91–104 (2005).
  • Michell AW, Lewis SJG, Foltynie T, Barker RA. Biomarkers and Parkinson’s disease. Brain127(8), 1693–1705 (2004).
  • Parkinson Study Group. The TEMPO study. A controlled trial of rasagiline in early Parkinson’s disease. Arch. Neurol.59(12), 1937–1943 (2002).
  • Stern MB, Marek KL, Friedman J et al. Double-blind, randomized, controlled trial of rasagiline as monotherapy in early Parkinson’s disease patients. Mov. Dis.19(8), 916–923 (2004).
  • Rascol O, Brooks DJ, Melamed E et al. Rasagiline as an adjunct to levodopa in patients with Parkinson’s disease and motor fluctuations (LARGO, Lasting effect in Adjunct therapy with Rasagiline Given Once daily study): a randomized, double-blind, parallel-group trial. Lancet365(9463), 947–954 (2005).
  • Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch. Neurol.62(2), 241–249 (2005).
  • Parkinson Study Group. A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol.61(4), 561–566 (2004).
  • Clarke CE. Neuroprotection and pharmacotherapy for motor symptoms in Parkinson’s disease. Lancet Neurol.3(8), 466–474 (2004).
  • Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA287(13), 1653–1661 (2002).
  • Whone A, Watts R, Stoessl J et al. Slower progression of Parkinson’s disease with ropinirole versus levodopa; the REAL-PET study. Ann. Neurol.54(1), 93–101 (2003).
  • Jesse S, Steinacker P, Lehnert S, Gillardon F, Hengerer B, Otto M. Neurochemical approaches in the laboratory diagnosis of Parkinson and Parkinson dementia syndromes: a review. CNS Neurosci. Ther.15(2), 157–182 (2009).
  • Tokuda T, Alem SA, Alsop D et al. Decreased α-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson’s disease. Biochem. Biophys. Res. Commun.349(1), 162–165 (2006).
  • Waragai M, Wei J, Fujita M et al. Increased level of DJ-1 in the cerebrospinal fluids of sporadic Parkinson’s disease. Biochem. Biophys. Res. Commun.345(3), 967–972 (2006).
  • Waragai M, Nakai M, Wei J et al. Increased level of DJ-1 as a possible marker for progression of sporadic Parkinson’s disease. Neurosci. Lett.425(1), 18–22 (2007).
  • Naoi M, Maruyama W. Mitochondria and survival and death of dopamine neurons. Presented at: Dopamine 50 Years. Göteborg, Sweden 30 May–2 June 2007.
  • Naoi M, Maruyama W, Riederer P. Cellular and animal models of Parkinson’s disease: a novel role of neuromelanin in degeneration of nigral dopamine neurons and finding of markers for neuroprotection. Presented at: The XXVI Collegium Internationale Neuro-psychopharmacologicum (CINP Congress). Munich, Germany 13–17 July 2008.
  • Sanz E, Quintana A, Battaglia V et al. Anti-apoptotic effect of MAO-B inhibitor PF9601N [N-(2-propynyl)-2-(5-benzyloxyl-indolyl), methylamine] is meditated by p53 pathway inhibition in MPP+-treated SH-SY5Y human dopaminergic cells. J. Neurochem.105(6), 2405–2417 (2008).
  • Chimenti F, Bolasco A, Manna F. et al. Synthesis, biological evaluation and 3D-QSAR of 1,3,5-trisubstituted-4,5-dihydro-(1H)-pyrazole derivatives as potent and highly selective monoamine oxidase A inhibitors. Curr. Med. Chem.13(12), 1411–1428 (2006).
  • Regina GL, Silverstri R, Artico M et al. New pyrrole inhibitors of monoamine oxidase: synthesis, biological evaluation, and structural determinations of MAO-A and MAO-B selectivity. J. Med. Chem.50(5), 922–931 (2007).
  • Binda C, Wang J, Pisani L, Caccia C et al. Structures of human oxidase B complexes with selective noncovalent inhibitors: sulfinamide and coumarin analogs. J. Med. Chem.50(23), 5848–5852 (2007).
  • Gallardo-Godoy A, Fierri A et al. Sulfur-substituted α-alkyl phenethylamines as selective and reversible MAO-A inhibitors: biological activities, CoMFA analysis, and active site modeling. J. Med. Chem.48(7), 2407–2419 (2005).
  • Regina GL, Silvestri R, Gatti V et al. Synthesis, structure–activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B. Bioorg. Med. Chem.16(22), 9729–9740 (2008).
  • Binda C, Wang J, Li M, Hubalek F, Mattevi A, Edmonson DE. Structural and mechanistic studies of aryalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry47(20), 5616–5625 (2008).
  • Youdim MBH, Buccafusco JJ. CNS targets for multi-functional drugs in the treatment of Alzheimer’s and Parkinson’s diseases. J. Neural Transm.112(4), 519–537 (2005).
  • Van der Schyf C, Geldenhuys WJ, Youdim MBH. Mutlifunctional drugs with different CNS targets for neuropsychiatric disorders. J. Neurochem.99(4), 1033–1048 (2006).
  • Tsunekawa H, Noda Y, Mouri A, Yoneda F, Nabeshima T. Synergistic effects of selegiline and donepezil on cognitive impairment induced by amyloid β (25–35). Behavior. Brain Res.190(2), 224–232 (2008).
  • Sagi Y, Drigues N, Youdim MB. The neurochemical and behavioral effects of the novel cholinesterase-monoamine oxidase inhibitor, ladostigil, in response to L-dopa and L-tryptophan, in rats. Br. J. Pharmacol.146(4), 553–560 (2005).
  • Bar-Am O, Weinreb O, Amit T, Youdim MB. The novel cholinesterase-monoamine oxidase inhibitor and anti-oxidant, ladostigil, confers neuroprotection in neuroblastoma cells and aged rats. J. Mol. Neurosci.37(2), 135–145 (2009).
  • Mandel S, Amit T, Bar-Am O, Youdim MBH. Iron dysregulation in Alzheimer’s disease; multimodal brain permeable iron chelating drugs, possessing neuroprotective–neurorescue and amyloid precursor protein-processing regulatory activities as therapeutic agents. Prog. Neurobiol.82(6), 348–360 (2007).
  • Shacar DB, Kahana N, Kampel V, Warshawsky A, Youdim MB. Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lesion in rats. Neuropharmacology46(2), 254–263 (2004).
  • Zheng H, Weiner LM, Bar-Am O et al. Design, synthesis, and evaluation of novel bifunctional iron-chelators, as potential agents for neuroprotecti in vivo on in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases. Bioorg. Med. Chem.13(3), 773–783 (2005).
  • Gal S, Zheng H, Fridkin M, Youdim MBH. Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion. J. Neurochem.95(1), 79–88 (2005).
  • Zhu W, Xie W, Pan T et al. Prevention and restoration of lactacystin-induced nigro–striatal dopamine neuron degeneration by novel-permeable iron chelators. FAESB J.21(14), 3835–3844 (2007).
  • Yogev-Falach M, Amit T, Bar-Am O, Youdim MBH. The importance of propargylamine moiety in the anti-Parkinson drug rasagiline and its derivatives for MAPK-dependent amyloid precursor protein processing. FASEB J.17(15), 23225–23227 (2003).
  • Amit T, Avramovich-Tirosh Y, Youdim MB, Mandel S. Targeting multiple Alzheimer’s disease etiologies with multimodel neuroprotective and neurorestorative iron chelators. FASEB J.22(5), 1296–1305 (2007).
  • Bar Am O, Amit T, Youdim MBH. Contrasting neuroprotective and neurotoxic actions of respective metabolites of anti-Parkinson drugs rasagiline and selegiline. Neurosci. Lett.355(3), 169–172 (2004).
  • Mandel S, Amit T, Kalfon L, Youdim MBH. Applying transcritomic and proteomic knowledge to Parkinson’s disease drug discovery. Expert Opin. Drug Discov.2(9), 1–16 (2009).
  • Kupsch A, Sautter J, Götz ME et al. Monoamine oxidase-inhibition and MPTP-induced neurotoxicity in the non-human primate: comparison of rasagiline (TV-1012) with selegiline. J. Neural Transm.108(8-9), 985–1009 (2001).
  • Eliash S, Sehteter N, Eilam R. Neuroprotective effect of rasagiline, a monoamine oxidase-B inhibitor, on spontaneous cell degeneration in a rat model J. Neural Transm.112(8) 991–1003 (2005).
  • Eliash J, Dror V, Cohen S, Behavi M. Neuroprotection by rasagiline in thiamine deficient rats. Brain Res.1256, 138–148 (2009).
  • Srefanova N, Poewe W, Wenning GK. Rasagiline is neuroprotective in a transgenic model of multiple system sclerosis. Exp. Neurol.210(2) 421–427 (2007).
  • Maruyama W, Akao Y, Youdim MB, Naoi M. Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022. J. Neural Transm. Suppl.60, 171–186 (2000)
  • Maruyama W, Youdim MB, Naoi M. Antiapoptotic properties of rasagiline, N-propargyl-1(R )-aminoindan, and its optical (S)-enaniomer. Ann. NY Acad. Sci.939, 320–329 (2001)
  • Abu-Raya S, Tabakman R, Blaugrund E, Trembovier V, Lazarovici P. Neuroprotective and neurotoxic effects of monoamine oxidase-B inhibitors and derived metabolites under ischemia in PC12 cells. Eur. J. Pharmacol.434(3) 109–116 (2002).
  • Bonneh-Barkay D, Ziv N, Finberg JP. Characterization of the neuroprotective activity of rasagiline in cerebellar granule cells. Neuropharmacology48(3) 406–416 (2005).
  • Kleiner Y, Bar-Am O, Amit T et al. TV1022 and propargylamine protect neonatal rat ventricular myocytes against doxorubicin-induced and serum starvation-induced cardiotoxicity. J. Cardiovasc. Pharmacol.52(3) 268–277 (2008).
  • Bar-Am O, Weinreb O, Amit T, Youdim MB. Regulation of Bcl-2 family proteins, neurotrophic factors, and APP processing in the neuroresue activity of propargylamines. FASEB J.19(13) 1899–1901 (2005).
  • Sagi Y, Weinstock M, Youdim MB. Attenuation of MPTP-induced dopaminergic neuotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor. J. Neurochem.86(2) 190–197 (2003).
  • Weinreb O, Bar-Am O, Amit T, Driques N, Sagi Y, Youdim MB. The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity. Chem. Biol. Interact.175(1-3) 318-–326 (2008).
  • Haberle D, Szökö E, Halasz AS, Magyar K. The effect of low doses of (-)-deprenyl and its metabolites on DSP-4 toxicity. J. Neural Transm.108(11) 1239–1247 (2001).
  • Hobbenaghi R, Tiraihi T. Neuroprotective effect of deprenyl in sensory neurons of axotomized dorsal root ganglion. Clin. Nuropharmacol.26(5) 263–269 (2003).
  • Kiray M, Bagriyanik HA, Pekcetin C, Ergur BU, Uysal N. Protective effects of deprenyl in transient cerebral ischemia in rats. Clin. J. Physiol.51(5) 275–281 (2008).
  • He KJ, Uetsuka K, Nakayama H, Neural progenitor cells are protected against MPTP by MAO-B inhibitors. Neurotoxicology29(6) 1141–1146 (2008).
  • Saravanan KS, Sindhu KM, Senthikumar KS, Mohanakumar KP. L-deprenyl protects against rotenone-induced, oxidative-stress-mediated dopaminergic neurodegeneration in rats. Neurocehm. Int.49(1) 28–40 (2006).
  • Maruyama W, Naoi M. Neuroprotection by (-)-deprenyl and related compounds. Mech. Ageing Dev.111(2-3) 189–200 (1999).
  • Naoi M, Maruyama W, Yagi K, Youdim M. Anti-apoptotic function of (-)-deprenyl (Selegiline) and related compounds. Neurobiology (Bp)8(1) 69–80 (2000).
  • Chetsawang B, Kooncumchoo P, Govitrapong P, Ebadi M. 1-Methyl-4-phenyl-pyridinium ion-induced oxidative stress, c-Jun phosphorylation and DNA fragmentation factor-45 cleavage in SK-N-SH cells are averted by selegiline. Neurochem. Int.53(6–8) 283–288 (2008).
  • Müller T, Przuntek H, Rieks M, Mackowiak A. Selegiline reduces cisplatin-induced neuronal death in neuroblastoma cells. Neurol. Res.30(4) 417–419 (2008).
  • Andringa G, Eshuis S, Perentes E et al. TCH346 prevents motor symptoms and loss of striatal FDOPA uptake in bilaterally MPTP-treated primates. Neurobiol. Dis.14(2) 205–217 (2003).
  • Sagot Y, Toni N, Perrelet D et al. An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease. Br. J. Pharmacol.131(4) 721–728 (2000).
  • Youdim MB, Gross A, Finberg JP. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br. J. Pharmacol.132(2) 500–506 (2001).
  • Wu RM, Chiueh CC, Pert A, Murphy DL. Apparent antioxidant effect of l-deprenyl on hydroxyl radical formation and nigral injury elicited by MPP+ in vivo. Eur. J. Pharmacol.243(3) 241–247 (1993).
  • Carrillo MC, Kanai S, Nokubo M, Kitani K, (-)Deprenyl induces activities of both superoxide dismutase and catalase but not glutathione peroxidase in the striatum of young male rats. Life Sci.48(6) 517–521 (1991).
  • Heikkila RE, Hess A, Duvoisin RC. Dopaminergic neurotoxicity of 1-methl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Science224(4656) 1451–1453 (1984).

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