Skip to main content

Advertisement

SpringerLink
Log in

L-DOPA treatment from the viewpoint of neuroprotection

Possible mechanism of specific and progressive dopaminergic neuronal death in Parkinson’s disease

  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

With regard to the mechanism of selective dopaminergic neuronal death, experimental results of studies on the neurotoxicity of MPTP and rotenone indicate that degeneration of dopamine neurons is closely related to mitochondrial dysfunction, inflammatory process and oxidative stress, particularly with regard to the generation of quinones as dopamine neuron-specific oxidative stress. Thus, it is now clear that the presence of high levels of discompart-mentalized free dopamine in dopaminergic neurons may explain the specific vulnerability of dopaminergic neurons through the generation of highly toxic quinones.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ambani LM, Van Woert MH, Murphy S (1975) Brain peroxidase and catalase in Parkinson’s disease. Arch Neurol 32:114–118

    PubMed  Google Scholar 

  2. Asanuma M, Miyazaki I, Ogawa N (2003) Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson’s disease. Neurotox Res 5:165–176

    PubMed  Google Scholar 

  3. Asanuma M, Miyazaki I, Ogawa N (2004) Neuroprotective effects of nonsteroidal anti-inflammatory drugs on neurodegenerative diseases. Curr Pharmac Design 10:695–700

    Article  Google Scholar 

  4. Baez S, Linderson Y, Segura-Aguilar J (1995) Superoxide dismutase and catalase enhance autoxidation during oneelectron reduction of aminochrome by NADPH-cytochrome P-450 reductase. Biochem Mol Med 54:12–18

    Article  PubMed  Google Scholar 

  5. Baez S, Segura-Aguilar J, Widersten M, Johansson AS, Mannervik B (1997) Glutathione transferases catalyse the detoxication of oxidized metabolites (o-quinones) of catecholamines and may serve as an antioxidant system preventing degenerative cellular processes. Biochem J 324:25–28

    PubMed  Google Scholar 

  6. Benathan M, Labidi F (1996) Cysteine-dependent 5-S-cysteinyldopa formation and its regulation by glutathione in normal epidermal melanocytes. Arch Dermatol Res 288:697–702

    Article  PubMed  Google Scholar 

  7. Berman SB, Hastings TG (1999) Dopamine oxidation alters mitochondrial respiration and induces permeability transition in brain mitochondria: implications for Parkinson’s disease. J Neurochem 73:1127–1137

    Article  PubMed  Google Scholar 

  8. Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson’s disease. Nat Neurosci 3:1301–1306

    Article  PubMed  Google Scholar 

  9. Bindoff LA, Birch-Machin M, Cartlidge NEF, Parker JR, Turnbull DM (1989) Mitochondrial function in Parkinson’s disease. Lancet ii:49

    Article  Google Scholar 

  10. Castano A, Herrera AJ, Cano J, Machado A (1998) Lipopolysaccharide intranigral injection induces inflammatory reaction and damage in nigrostriatal dopaminergic system. J Neurochem 70:1584–1592

    PubMed  Google Scholar 

  11. Choi HJ, Kim SW, Lee SY, Hwang Q (2003) Dopamine-dependent cytotoxicity of tetrahydrobiopterin: a possible mechanism for selective neurodegeneration in Parkinson’s disease. J Neurochem 86:143–152

    Article  PubMed  Google Scholar 

  12. Chung KK, Dawson VL, Dawson TM (2001) The role of the ubiquitin-proteasomal pathway in Parkinson’s disease and other neurodegenerative disorders. Trends Neurosci 24:S7–S14

    Article  PubMed  Google Scholar 

  13. Conway KA, Lee SJ, Rochet JC, Ding TT, Williamson RE, Lansbury PT Jr (2000) Acceleration of oligomerization, not fibrillization, is a shared property of both a-synuclein mutations linked to early-onset Parkinson’s disease: implications for pathogenesis and therapy. Proc Natl Acad Sci USA 97:571–576

    Article  PubMed  Google Scholar 

  14. Conway KA, Rochet JC, Bieganski RM, Lansbury PT Jr (2001) Kinetic stabilization of the a-synuclein protofibril by a dopamine-a-synuclein adduct. Science 294:1346–1349

    Article  PubMed  Google Scholar 

  15. Dabbeni-Sala F, Di Santo S, Franceschini D, Skaper SD, Giusti P (2001) Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity. Faseb J 15:164–170

    Article  PubMed  Google Scholar 

  16. Dexter DT, Wells FR, Lees AJ, Agid Y, Jenner P, Marsden CD (1989) Increase nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52:1830–1836

    PubMed  Google Scholar 

  17. Diaz-Corrales FJ, Asanuma M, Miyazaki I, Ogawa N (2004) Rotenone induces disassembly of the Golgi apparatus in the rat dopaminergic neuroblastoma B65 cell line. Neurosci Lett 354:59–63

    Article  PubMed  Google Scholar 

  18. Drukarch B, van Muiswinkel FL (2000) Drug treatment of Parkinson’s disease. Time for phase II. Biochem Pharmacol 59:1023–1031

    Article  PubMed  Google Scholar 

  19. Duffy S, So A, Murphy TH (1998) Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage. J Neurochem 71:69–77

    PubMed  Google Scholar 

  20. Elkon H, Melamed E, Offen D (2001) 6-Hydroxydopamine increases ubiquitin-conjugates and protein degradation: implications for the pathogenesis of Parkinson’s disease. Cell Mol Neurobiol 21:771–781

    Article  PubMed  Google Scholar 

  21. Foppoli C, Coccia R, Cini C, Rosei MA (1997) Catecholamines oxidation by xanthine oxidase. Biochim Biophys Acta 1334:200–206

    PubMed  Google Scholar 

  22. Fornai F, Lenzi P, Gesi M, Ferrucci M, Lazzeri G, Busceti CL, Ruffoli R, Soldani P, Ruggieri S, ASlessandri MG, Paparelli A (2003) Fine structure and biochemical mechanisms underlying nigrostriatal inclusions and cell death after proteasome inhibition. J Neurosci 23:8955–8966

    PubMed  Google Scholar 

  23. Fornstedt B, Rosengren E, Carlsson A (1986) Occurrence and distribution of 5-S-cysteinyl derivatives of dopamine, dopa and dopac in the brains of eight mammalian species. Neuropharmacology 25:451–454

    Article  PubMed  Google Scholar 

  24. Gao HM, Hong JS, Zhang W, Liu B (2002) Distinct role for microglia in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 22:782–790

    PubMed  Google Scholar 

  25. Gao HM, Jiang J, Wilson B, Zhang W, Hong JS, Liu B (2002) Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson’s disease. J Neurochem 81:1285–1297

    Article  PubMed  Google Scholar 

  26. Gao HM, Liu B, Hong JS (2003) Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons. J Neurosci 23:6181–6187

    PubMed  Google Scholar 

  27. Gao HM, Liu B, Zhang W, Hong JS (2003) Novel anti-inflammatory therapy for Parkinson’s disease. Trends Pharmacol Sci 24:395–401

    Article  PubMed  Google Scholar 

  28. Glinka Y, Gassen M, Youdim MB (1997) Mechanism of 6-hydroxydopamine neurotoxicity. J Neural Transm 50 (Suppl):55–66

    Google Scholar 

  29. Glinka YY, Youdim MB (1995) Inhibition of mitochondrial complexes I and IV by 6-hydroxydopamine. Eur J Pharmacol 292:329–332

    PubMed  Google Scholar 

  30. Graham DG (1978) Oxidative pathways for catecholamines in the genesis of neuromelanin and cytotoxic quinones. Mol Pharmacol 14:633–643

    PubMed  Google Scholar 

  31. Haque ME, Asanuma M, Higashi Y, Miyazaki I, Tanaka K, Ogawa N (2003) Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive quinone generation in neuroblastoma cells. Biochim Biophys Acta 1619:39–52

    PubMed  Google Scholar 

  32. Hara H, Ohta M, Ohta K, Kuno S, Adachi T (2003) Increase of antioxidative potential by tert-butylhydroquinone protects against cell death associated with 6-hydroxydopamine-induced oxidative stress in neuroblastoma SH-SY5Y cells. Mol Brain Res 119:125–131

    Article  PubMed  Google Scholar 

  33. Hastings TG (1995) Enzymatic oxidation of dopamine: the role of prostaglandin H synthase. J Neurochem 64:919–924

    PubMed  Google Scholar 

  34. Hoglinger GU, Carrard G, Michel PP, Medja F, Lombes A, Ruberg M, Friguet B, Hirsch EC (2003) Dysfunction of mitochondrial complex I and the proteasome: interactions between two biochemical deficits in a cellular model of Parkinson’s disease. J Neurochem 86:1297–1307

    PubMed  Google Scholar 

  35. Hunot S, Brugg B, Ricard D, Michel PP, Muriel M-P, Ruberg M, Faucheux B, Agid Y, Hirsch EC (1997) Nuclear translocation of NF-κB is increased in dopaminergic neurons of patients with Parkinson disease. Proc Natl Acad Sci USA 94:7531–7536

    Article  PubMed  Google Scholar 

  36. Hunot S, Hartmann A, Hirsch EC (2001) The inflammatory response in the Parkinson brain. Clin Neurosci Res 1:434–443

    Article  Google Scholar 

  37. Hunot S, Hirsch EC (2003) Neuroinflammatory processes in Parkinson’s disease. Ann Neurol 53:S49–S58; discussion S58–S60

    Article  PubMed  Google Scholar 

  38. Iida M, Miyazaki I, Tanaka K, Kabuto H, Iwata-Ichikawa E, Ogawa N (1999) Dopamine D2 receptor-mediated antioxidant and neuroprotective effects of ropinirole, a dopamine agonist. Brain Res 838:51–59

    Article  PubMed  Google Scholar 

  39. Inazu M, Kubota N, Takeda H, Zhang J, Kiuchi Y, Oguchi K, Matsumiya T (1999) Pharmacological characterization of dopamine transport in cultured rat astrocytes. Life Sci 64:2239–2245

    Article  PubMed  Google Scholar 

  40. Inazu M, Takeda H, Ikoshi H, Uchida Y, Kubota N, Kiuchi Y, Oguchi K, Matsumiya T (1999) Regulation of dopamine uptake by basic fibroblast growth factor and epidermal growth factor in cultured rat astrocytes. Neurosci Res 34:235–244

    Article  PubMed  Google Scholar 

  41. Ito S, Fujita K (1982) Conjugation of dopa and 5-S-cysteinyldopa with cysteine mediated by superoxide radical. Biochem Pharmacol 31:2887–2889

    Article  PubMed  Google Scholar 

  42. Jara JR, Aroca P, Solano F, Martinez JH, Lozano JA (1988) The role of sulfhydryl compounds in mammalian melanogenesis: the effect of cysteine and glutathione upon tyrosinase and the intermediates of the pathway. Biochim Biophys Acta 967:296–303

    PubMed  Google Scholar 

  43. Juorio AV, Li XM, Walz W, Paterson IA (1993) Decarboxylation of L-dopa by cultured mouse astrocytes. Brain Res 626:306–309

    Article  PubMed  Google Scholar 

  44. Keller JN, Huang FF, Dimayuga ER, Maragos WF (2000) Dopamine induces proteasome inhibition in neural PC12 cell line. Free Radic Biol Med 29:1037–1042

    Article  PubMed  Google Scholar 

  45. Kish SJ, Morito C, Hornykiewicz O (1985) Glutathione peroxidase activity in Parkinson’s disease. Neurosci Lett 58:343–346

    Article  PubMed  Google Scholar 

  46. Knott C, Stern G, Wilkin GP (2000) Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol Cell Neurosci 16:724–739

    Article  PubMed  Google Scholar 

  47. Korytowski W, Sarna T, Kalyanaraman B, Sealy RC (1987) Tyrosinase-catalyzed oxidation of dopa and related catechol(amine)s: a kinetic electron spin resonance investigation using spin-stabilization and spin label oximetry. Biochim Biophys Acta 924:383–392

    PubMed  Google Scholar 

  48. Kuhn DM, Arthur RE, Jr., Thomas DM, Elferink LA (1999) Tyrosine hydroxylase is inactivated by catecholquinones and converted to a redoxcycling quinoprotein: possible relevance to Parkinson’s disease. J Neurochem 73:1309–1317

    Article  PubMed  Google Scholar 

  49. Kurkowska-Jastrzebska I, Wronska A, Kohutnicka M, Czlonkowski A, Czlonkowska A (1999) The inflammatory reaction following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication in mouse. Exp Neurol 156:50–61

    Article  PubMed  Google Scholar 

  50. Lai CT, Yu PH (1997) Dopamine- and L-b-3,4-dihydroxyphenylalanine hydrochloride (L-Dopa)-induced cytotoxicity towards catecholaminergic neuroblastoma SH-SY5Y cells. Effects of oxidative stress and antioxidative factors. Biochem Pharmacol 53:363–372

    Article  PubMed  Google Scholar 

  51. Langston JW, Forno LS, Tetrud J, Reeves AG, Kaplan JA, Karluk D (1999) Evidence of active nerve cell degeneration in the substantia nigra of humans years after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure. Ann Neurol 46:598–605

    Article  PubMed  Google Scholar 

  52. LaVoie MJ, Hastings TG (1999) Peroxynitrite-and nitrite-induced oxidation of dopamine: implications for nitric oxide in dopaminergic cell loss. J Neurochem 73:2546–2554

    Article  PubMed  Google Scholar 

  53. Le WD, Jankovic J, Xie W, Appel SH (2000) Antioxidant property of pramipexole independent of dopamine receptor activation in neuroprotection. J Neural Transm 107:1165–1173

    Article  PubMed  Google Scholar 

  54. Li XM, Juorio AV, Paterson IA, Walz W, Zhu MY, Boulton AA, Inazu M, Takeda H, Matsumiya T (1992) Gene expression of aromatic L-amino acid decarboxylase in cultured rat glial cells. J Neurochem 59:1172–1175

    PubMed  Google Scholar 

  55. Lizasoain I, Moro MA, Knowles RG, Darley UV, Moncada S (1996) Nitric oxide and peroxynitrite exert distinct effects on mitochondrial respiration which are differentially blocked by glutathione or glucose. Biochem J 314:877–880

    PubMed  Google Scholar 

  56. Mattammal MB, Strong R, Lakshmi VM, Chung HD, Stephenson AH (1995) Prostaglandin H synthetase-mediated metabolism of dopamine: implication for Parkinson’s disease. J Neurochem 64:1645–1654

    PubMed  Google Scholar 

  57. McGeer PL, Itagaki S, Boyes B, McGeer EG (1988) Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson’s and Alzheimer’s disease brains. Neurology 38:1285–1291

    PubMed  Google Scholar 

  58. McNaught KS, Belizaire R, Isacson O, Jenner P, Olanow CW (2003) Altered proteasomal function in sporadic Parkinson’s disease. Exp Neurol 179:38–46

    Article  PubMed  Google Scholar 

  59. McNaught KS, Belizaire R, Jenner P, Olanow CW, Isacson O (2002) Selective loss of 20S proteasome alpha-subunits in the substantia nigra pars compacta in Parkinson’s disease. Neurosci Lett 326:155–158

    Article  PubMed  Google Scholar 

  60. McNaught KS, Bjorklund LM, Belizaire R, Isacson O, Jenner P, Olanow CW (2002) Proteasome inhibition causes nigral degeneration with inclusion bodies in rats. Neuroreport 13:1437–1441

    Article  PubMed  Google Scholar 

  61. McNaught KS, Jenner P (2001) Proteasomal function is impaired in substantia nigra in Parkinson’s disease. Neurosci Lett 297:191–194

    Article  PubMed  Google Scholar 

  62. McNaught KS, Mytilineou C, Jnobaptiste R, Yabut J, Shashidharan P, Jennert P, Olanow CW (2002) Impairment of the ubiquitin-proteasome system causes dopaminergic cell death and inclusion body formation in ventral mesencephalic cultures. J Neurochem 81:301–306

    Article  PubMed  Google Scholar 

  63. McNaught KS, Olanow CW (2003) Proteolytic stress: a unifying concept for the etiopathogenesis of Parkinson’s disease. Ann Neurol 53:S73–S84; discussion S84–S76

    Article  PubMed  Google Scholar 

  64. McNaught KS, Olanow CW, Halliwell B, Isacson O, Jenner P (2001) Failure of the ubiquitin-proteasome system in Parkinson’s disease. Nat Rev Neurosci 2:589–594

    Article  PubMed  Google Scholar 

  65. Meyer M, Schreck R, Baeuerle PA (1993) H2O2 and antioxidants have opposite effects on activation of NF-kB and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J 12:2005–2015

    PubMed  Google Scholar 

  66. Mizuno Y, Ohta S, Tanaka M, Takamiya S, Suzuki K, Sato T, Oya H, Ozawa T, Kagawa Y (1989) Deficiencies in complex I subunits of the respiratory chain in Parkinson’s disease. Biochem Biophys Res Commun 163:1450–1455

    Article  Google Scholar 

  67. Mizuno Y, Sone N, Saitoh T (1987) Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 1-methyl-4-phenylptridinium ion on activities of the enzymes in the electron transport in mouse brain. J Neurochem 48:1787–1793

    PubMed  Google Scholar 

  68. Munday R, Smith BL, Munday CM (1998) Effects of butylated hydroxyanisole and dicoumarol on the toxicity of menadione to rats. Chem Biol Interact 108:155–170

    Article  PubMed  Google Scholar 

  69. Muralikrishnan D, Mohanakumar KP (1998) Neuroprotection by bromocriptine against 1-methyl-4-phenyl-1,2,3,6-tetrwhydropyridine-induced neurotoxicity in mice. FASEB J 12:905–912

    PubMed  Google Scholar 

  70. Nagatsu T (2002) Parkinson’s disease: changes in apoptosis-related factors suggesting possible gene therapy. J Neural Transm 109:731–745

    Article  PubMed  Google Scholar 

  71. Nagatsu T, Mogi M, Ichinose H, Togari A (2000) Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm 58(Suppl):277–290

    Google Scholar 

  72. O’Neill LAJ, Kaltschmidt C (1997) NF-κB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 20:252–258

    Article  PubMed  Google Scholar 

  73. Offen D, Ziv I, Sternin H, Melamed E, Hochman A (1996) Prevention of dopamine-induced cell death by thiol antioxidants: Possible implications for treatment of Parkinson’s disease. Exp Neurol 141:32–39

    Article  PubMed  Google Scholar 

  74. Pardo B, Mena MA, Casarejos MJ, Paino CL, De Yebenes JG (1995) Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants. Brain Res 682:133–143

    Article  PubMed  Google Scholar 

  75. Paris I, Dagnino-Subiabre A, Marcelain K, Bennett LB, Caviedes P, Caviedes R, Azar CO, Segura-Aguilar J (2001) Copper neurotoxicity is dependent on dopamine-mediated copper uptake and one-electron reduction of aminochrome in a rat substantia nigra neuronal cell line. J Neurochem 77:519–529

    Article  PubMed  Google Scholar 

  76. Perry TL, Yong VW (1986) Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett 67:269–274

    Article  PubMed  Google Scholar 

  77. Ramsay RR, Singer TP (1986) Energy dependent uptake of MPP+, the neurotoxic metabolite of MPTP, by mitochondria. J Biol Chem 261:7585–7587

    PubMed  Google Scholar 

  78. Riederer P, Sofic E, Rausch WD, Schmidt B, Reynolds GP, Kellinger K, Youdim MBH (1989) Transition metals, ferritin, glutathione, and ascorbic acid in parkinsonian brains. J Neurochem 52:515–520

    PubMed  Google Scholar 

  79. Rosei MA, Blarzino C, Foppoli C, Mosca L, Coccia R (1994) Lipoxygenase-catalyzed oxidation of catecholamines. Biochem Biophys Res Commun 200:344–350

    Article  PubMed  Google Scholar 

  80. Ryu EJ, Harding HP, Angelastro JM, Vitolo OV, Ron D, Greene LA (2002) Endoplasmic reticulum stress and the unfolded protein response in cellular models of Parkinson’s disease. J Neurosci 22:10690–10698

    PubMed  Google Scholar 

  81. Sakka N, Sawada H, Izumi Y,Kume T, Katsuki H, Kaneko S, Shimohama S, Akaike A (2003) Dopamine is involved in selectivity of dopaminergic neuronal death by rotenone. Neuroreport 14:2425–2428

    Article  PubMed  Google Scholar 

  82. Sampaio-Maia B, Serrao MP, Soaresda-Silva P (2001) Regulatory pathways and uptake of L-DOPA by capillary cerebral endothelial cells, astrocytes, and neuronal cells. Am J Physiol Cell Physiol 280:C333–C342

    PubMed  Google Scholar 

  83. Sawada H, Kohno R,Kihara T, Izumi Y, Sakka N, Ibi M, Nakanishi M, Nakamizo T, Yamakawa K, Shibasaki H, Yamamoto N, Akaike A, Inden M, Kitamura Y, Taniguchi T, Shimohama S (2004) Proteasome mediates dopaminergic neuronal degeneration, and its inhibition causes alpha-synuclein inclusions. J Biol Chem 279:10710–10719

    Article  PubMed  Google Scholar 

  84. Schapira AH, Cooper JM, Dexter D, Clark JB, Jenner P, Marsden CD (1990) Mitochondrial complex I deficiency in Parkinson’s disease. J Neurochem 54:823–827

    PubMed  Google Scholar 

  85. Segura-Aguilar J, Baez S, Widersten M, Welch CJ, Mannervik B (1997) Human class Mu glutathione transferases, in particular isoenzyme M2-2, catalyze detoxication of the dopamine metabolite aminochrome. J Biol Chem 272:5727–5731

    Article  PubMed  Google Scholar 

  86. Segura-Aguilar J, Metodiewa D, Welch CJ (1998) Metabolic activation of dopamine o-quinones to o-semiquinones by NADPH cytochrome P450 reductase may play an important role in oxidative stress and apoptotic effects. Biochim Biophys Acta 1381:1–6

    PubMed  Google Scholar 

  87. Sherer TB, Betarbet R, Kim JH, Greenamyre JT (2003) Selective microglial activation in the rat rotenone model of Parkinson’s disease. Neurosci Lett 341:87–90

    Article  PubMed  Google Scholar 

  88. Sherer TB, Betarbet R, Stout AK, Lund S, Baptista M, Panov AV, Cookson MR, Greenamyre JT (2002) An in vitro model of Parkinson’s disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci 22:7006–7015

    PubMed  Google Scholar 

  89. Simpson CS, Morris BJ (1999) Activation of nuclear factor kB by nitric oxide in rat striatal neurones: differential inhibition of the p50 and p65 subunits by dexamethasone. J Neurochem 73:353–361

    Article  PubMed  Google Scholar 

  90. Spencer JP, Jenner P, Daniel SE, Lees AJ, Marsden DC, Halliwell B (1998) Conjugates of catecholamines with cysteine and GSH in Parkinson’s disease: possible mechanisms of formation involving reactive oxygen species. J Neurochem 71:2112–2122

    PubMed  Google Scholar 

  91. Stern EL, Quan N, Proescholdt MG, Herkenham M (2000) Spatiotemporal induction patterns of cytokine and related immune signal molecule mRNAs in response to intrastriatal injection of lipopolysaccharide. J Neuroimmunol 109:245–260

    Article  PubMed  Google Scholar 

  92. Sulzer D, Bogulavsky J, Larsen KE, Behr G, Karatekin E, Kleinman MH, Turro N, Krantz D, Edwards RH, Greene LA, Zecca L (2000) Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles. Proc Natl Acad Sci USA 97:11869–11874

    Article  PubMed  Google Scholar 

  93. Sulzer D, Zecca L (2000) Intraneuronal dopamine-quinone synthesis: a review. Neurotox Res 1:181–195

    PubMed  Google Scholar 

  94. Tanaka K, Miyazaki I, Fujita N, Haque ME, Asanuma M, Ogawa N (2001) Molecular mechanism in activation of glutathione system by ropinirole, a selective dopamine D2 agonist. Neurochem Res 26:31–36

    Article  PubMed  Google Scholar 

  95. The Parkinson SG (1989) Effects of deprenyl on progression of disability in early Parkinson’s disease. N Engl J Med 321:1364–1371

    PubMed  Google Scholar 

  96. Tsai MJ, Lee EH (1996) Characterization of L-DOPA transport in cultured rat and mouse astrocytes. J Neurosci Res 43:490–495

    Article  PubMed  Google Scholar 

  97. Tse DC, McCreery RL, Adams RN (1976) Potential oxidative pathways of brain catecholamines. J Med Chem 19:37–40

    Article  PubMed  Google Scholar 

  98. Xu Y, Stokes AH, Roskoski R Jr, Vrana KE (1998) Dopamine, in the presence of tyrosinase, covalently modifies and inactivates tyrosine hydroxylase. J Neurosci Res 54:691–697

    Article  PubMed  Google Scholar 

  99. Yoshioka M, Tanaka K, Miyazaki I, Fujita N, Higashi Y, Asanuma M, Ogawa N (2002) The dopamine agonist cabergoline provides neuroprotection by activation of the glutashione system and scavenging free radicals. Neurosci Res 43:256–267

    Article  Google Scholar 

  100. Zoratti M, Szabo I (1995) The mitochondrial permeability transition. Biochim Biophys Acta 1241:139–176

    PubMed  Google Scholar 

  101. Ogawa N, Asanuma M, Miyoshi K (2004) Mechanism of specific dopaminergic neuronal death in Parkinson’s disease. Nippon Rinsho 62:1629–1634 (in Japanese with English abstract)

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Brain Science, Okayama University Graduate School of Medicine & Dentistry, Okayama 700-8558, Japan

    Norio Ogawa MD, PhD, Masato Asanuma, Ikuko Miyazaki, Francisco J. Diaz-Corrales & Ko Miyoshi

Authors
  1. Norio Ogawa MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masato Asanuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ikuko Miyazaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Francisco J. Diaz-Corrales
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ko Miyoshi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norio Ogawa MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogawa, N., Asanuma, M., Miyazaki, I. et al. L-DOPA treatment from the viewpoint of neuroprotection. J Neurol 252 (Suppl 4), iv23–iv31 (2005). https://doi.org/10.1007/s00415-005-4006-7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-4006-7

Key words

Search

Navigation