Neurological Sciences

, Volume 31, Issue 5, pp 531–540 | Cite as

Parkinson’s disease: oxidative stress and therapeutic approaches

Review Article


Parkinson’s disease (PD) is a neurodegenerative disorder, caused by reduced levels of catecholamines and oxidative stress. Symptoms seen in the disease include tremor, rigidity, bradykinesia and postural disability. Oxidative stress plays a key role in neurodegeneration and motor abnormalities seen in PD. Altered levels of the protein caused by these changes lead to defective ubiquitin–proteasome pathway. Neurodegeneration seen in PD and Canavan disease has a common mechanism. Recent studies suggest that herbal medicines can improve molecular changes and motor functions seen in PD.


Parkinson’s disease Antioxidant Withania somnifera Neurodegeneration Canavan disease 


  1. 1.
    Parkinson J (2002) An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 14:223–236PubMedGoogle Scholar
  2. 2.
    Anglade P, Vyas S, Javoy-Agid F, Herrero MT, Michel PP et al (1997) Apoptosis and autophagy in nigral neurons of patients with Parkinson’s disease. Histol Histopathol 12:25–31PubMedGoogle Scholar
  3. 3.
    Alam ZI, Jenner A, Daniel SE, Lees AJ, Cairns N et al (1997) Oxidative DNA damage in the parkinsonian brain; a selective increase in 8-hydroxyguanine in substantia nigra? J Neurochem 69:1196–1203PubMedCrossRefGoogle Scholar
  4. 4.
    Delaveau P, Salgado-Pineda P, Witjas T, Micallef-Roll J, Fakra E, Azulay JP, Blin O (2009) Dopaminergic modulation of amygdala activity during emotion recognition in patients with Parkinson disease. J Clin Psychopharmacol 29:548–554PubMedCrossRefGoogle Scholar
  5. 5.
    Rajasankar S, Manivasagam T, Surendran S (2009) Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson’s disease. Neurosci Lett 454:11–15PubMedCrossRefGoogle Scholar
  6. 6.
    Kim W, Erlandsen H, Surendran S, Stevens RC, Gamez A, Michols-Matalon K, Tyring SK, Matalon R (2004) Trends in enzyme therapy for phenylketonuria. Mol Ther 10:220–224PubMedCrossRefGoogle Scholar
  7. 7.
    Höglinger GU, Carrard G, Michel PP, Medja F, Lombès 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 86:1297–1307PubMedCrossRefGoogle Scholar
  8. 8.
    McNaught KS, Jenner P (2001) Proteasomal function is impaired in substantia nigra in Parkinson’s disease. Neurosci Lett 297:191–194PubMedCrossRefGoogle Scholar
  9. 9.
    Zimprich A, Biskup S, Leitner P, Lichtner P et al (2004) Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron 44:601–607PubMedCrossRefGoogle Scholar
  10. 10.
    Orth M, Schapira AH (2002) Mitochondrial involvement in Parkinson’s disease. Neurochem Int 40:533–541PubMedCrossRefGoogle Scholar
  11. 11.
    Gerlach M, Riederer P (2003) Current preclinical findings on substances against Parkinson’s disease. Nervenarzt 74:S2–S6PubMedCrossRefGoogle Scholar
  12. 12.
    Rajput AH, Sitte HH, Rajput A, Fenton ME, Pifl C, Hornykiewicz O (2008) Globus pallidus dopamine and Parkinson motor subtypes: clinical and brain biochemical correlation. Neurology 70:1403–1410PubMedCrossRefGoogle Scholar
  13. 13.
    Rajasankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, Surendran S (2009) Withania somnifera improves antioxidants, catecholamines and physiological abnormalities seen in a Parkinson’s disease model mouse. J Ethnopharmacol 125:369–373PubMedCrossRefGoogle Scholar
  14. 14.
    Deumens R, Blokland A, Prickaerts J (2002) Modeling Parkinson’s disease in rats: an evaluation of 6-OHDA lesions of the nigrostriatal pathway. Exp Neurol 175:303–317PubMedCrossRefGoogle Scholar
  15. 15.
    Keeney PM, Xie J, Capaldi RA, Bennett JP Jr (2006) Parkinson’s disease brain mitochondrial complex I has oxidatively damaged subunits and is functionally impaired and misassembled. J Neurosci 26:5256–5264PubMedCrossRefGoogle Scholar
  16. 16.
    Surendran S (2009) Upregulation of N-acetylaspartic acid alters inflammation, transcription and contractile associated protein levels in the stomach and smooth muscle contractility. Mol Biol Rep 36:201–206PubMedCrossRefGoogle Scholar
  17. 17.
    Dexter DT, Wells FR, Lees AJ, Agid F, Agid Y, Jenner P, Marsden CD (1989) Increased nigral iron content and alterations in other metal ions occurring in brain in Parkinson’s disease. J Neurochem 52:1830–1836PubMedCrossRefGoogle Scholar
  18. 18.
    Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 93:2696–2701PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, Montine TJ (1999) Parkinson’s disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154:1423–1429PubMedGoogle Scholar
  20. 20.
    Graham DG, Tiffany SM, Bell WR Jr, Gutknecht WF (1978) Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydroxydopamine, and related compounds toward C1300 neuroblastoma cells in vitro. Mol Pharmacol 14:644–653PubMedGoogle Scholar
  21. 21.
    Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B (1997) A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69:1326–1329PubMedCrossRefGoogle Scholar
  22. 22.
    Floor E, Wetzel MG (1998) Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay. J Neurochem 70:268–275PubMedCrossRefGoogle Scholar
  23. 23.
    Miao L, St Clair DK (2009) Regulation of superoxide dismutase genes: Implications in disease. Free Radic Biol Med 47:344–356PubMedCrossRefGoogle Scholar
  24. 24.
    Surendran S, Matalon R, Tyring SK (2007) Neurochemical changes and therapeutical targets in phenylketonuria (PKU). In: Surendran S (ed) Neurochemistry of metabolic diseases-lysosomal storage diseases, phenylketonuria and Canavan disease. Transworld Research Network, India, pp 105–118Google Scholar
  25. 25.
    Gałecka E, Jacewicz R, Mrowicka M, Florkowski A, Gałecki P (2008) Antioxidative enzymes—structure, properties, functions. Pol Merkur Lekarski 25:266–268PubMedGoogle Scholar
  26. 26.
    Martin HL, Teismann P (2009) Glutathione—a review on its role and significance in Parkinson’s disease. FASEB J 23(10):3263–3272PubMedCrossRefGoogle Scholar
  27. 27.
    Maker HS, Weiss C, Silides DJ, Cohen G (1981) Coupling of dopamine oxidation (monoamine oxidase activity) to glutathione oxidation via the generation of hydrogen peroxide in rat brain homogenates. J Neurochem 36:589–593PubMedCrossRefGoogle Scholar
  28. 28.
    Dexter DT, Carter CJ, Wells FR, Javoy-Agid F, Agid Y, Lees A, Jenner P, Marsden CD (1989) Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52:381–389PubMedCrossRefGoogle Scholar
  29. 29.
    Sofic E, Riederer P, Heinsen H, Beckmann H, Reynolds GP, Hebenstreit G, Youdim MB (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74:199–205PubMedCrossRefGoogle Scholar
  30. 30.
    Pearce PK, Owen A, Daniel S, Jenner P, Marsden CD (1997) Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease. J Neural Transm 104:661–677PubMedCrossRefGoogle Scholar
  31. 31.
    Sofic E, Lange KW, Jellinger K, Riederer KP (1992) Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson’s disease. Neurosci Lett 142:128–130PubMedCrossRefGoogle Scholar
  32. 32.
    Cole NN, Dieuliis D, Leo P, Mitchell DC, Nussbaum RL (2008) Mitochondrial translocation of alpha-synuclein is promoted by intracellular acidification. Exp Cell Res 314:2076–2089PubMedCrossRefGoogle Scholar
  33. 33.
    Shavali S, Brown-Borg HM, Ebadi M, Porter J (2008) Mitochondrial localization of alpha-synuclein protein in alpha-synuclein overexpressing cells. Neurosci Lett 439:125–128PubMedCrossRefGoogle Scholar
  34. 34.
    Palacino JJ, Sagi D, Goldberg MS, Krauss S, Motz C, Wacker M, Klose J, Shen J (2004) Mitochondrial dysfunction and oxidative damage in parkin-deficient mice. J Biol Chem 279:18614–18622PubMedCrossRefGoogle Scholar
  35. 35.
    Muftuoglu M, Elibol B, Dalmizrak O, Ercan A, Kulaksiz G, Ogüs H, Dalkara T, Ozer N (2004) Mitochondrial complex I and IV activities in leukocytes from patients with parkin mutations. Mov Disord 19:544–548PubMedCrossRefGoogle Scholar
  36. 36.
    Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G (2005) Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet 14:3477–3492PubMedCrossRefGoogle Scholar
  37. 37.
    Hoepken HH, Gispert S, Morales B, Wingerter O, Del Turco D, Mülsch A, Nussbaum RL, Müller K, Dröse S, Brandt T, Deller U, Wirth B, Kudin AP, Kunz WS, Auburger G (2007) Mitochondrial dysfunction, peroxidation damage and changes in glutathione metabolism in PARK6. Neurobiol Dis 25:401–411PubMedCrossRefGoogle Scholar
  38. 38.
    Zhang L, Shimoji M, Thomas B, Moore DJ, Yu SW, Marupudi NI, Torp R, Torgner IA, Ottersen OP, Dawson TM, Dawson VL (2005) Mitochondrial localization of the Parkinson’s disease related protein DJ-1: implications for pathogenesis. Hum Mol Genet 14:2063–2073PubMedCrossRefGoogle Scholar
  39. 39.
    Canet-Aviles RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci USA 101:9103–9108PubMedCrossRefGoogle Scholar
  40. 40.
    West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM (2005) Parkinson’s disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci USA 102:16842–16847PubMedCrossRefGoogle Scholar
  41. 41.
    Strauss KM, Martins LM, Plun-Favreau H, Marx FP, Kautzmann S, Berg D, Gasser T, Wszolek Z, Müller T, Bornemann A, Wolburg H, Downward J, Riess O, Schulz JB, Krüger R (2005) Loss of function mutations in the gene encoding Omi/HtrA2 in Parkinson’s disease. Hum Mol Genet 14:2099–2111PubMedCrossRefGoogle Scholar
  42. 42.
    Ravagnan L, Roumier T, Kroemer G (2002) Mitochondria, the killer organelles and their weapons. J Cell Physiol 192:131–137PubMedCrossRefGoogle Scholar
  43. 43.
    Penn AM, Roberts T, Hodder J, Allen PS, Zhu G, Martin WR (1995) Generalized mitochondrial dysfunction in Parkinson’s disease detected by magnetic resonance spectroscopy of muscle. Neurology 45:2097–2099PubMedGoogle Scholar
  44. 44.
    Baik H-M, Choe BY, Lee H-K, Suh T-S, Son BC, Lee J-M (2002) Metabolic alterations in Parkinson’s disease after thalamotomy, as revealed by H MR spectroscopy. Korean J Radiol 3:180–188PubMedCrossRefGoogle Scholar
  45. 45.
    Griffin TA, Nandi D, Cruz M, Fehling HJ, Kaer LV, Monaco JJ, Colbert RA (1998) Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits. J Exp Med 187:97–104PubMedCrossRefGoogle Scholar
  46. 46.
    Kingsbury DJ, Griffin TA, Colbert RA (2000) Novel propeptide function in 20 S proteasome assembly influences beta subunit composition. J Biol Chem 275:24156–24162PubMedCrossRefGoogle Scholar
  47. 47.
    Lindå H, Hammarberg H, Piehl F, Khademi M, Olsson T (1999) Expression of MHC class I heavy chain and beta2-microglobulin in rat brainstem motoneurons and nigral dopaminergic neurons. J Neuroimmunol 101:76–86PubMedCrossRefGoogle Scholar
  48. 48.
    Sawada M, Imamura K, Nagatsu T (2006) Role of cytokines in inflammatory process in Parkinson’s disease. J Neural Transm Suppl 70:373–381PubMedCrossRefGoogle Scholar
  49. 49.
    Surendran S (2001) Possible role of fas antigen (CD 95) in human amniotic epithelial cell death: an in vitro study. Cell Biol Int 25:485–488PubMedCrossRefGoogle Scholar
  50. 50.
    Chu Y, Dodiya H, Aebischer P, Olanow CW, Kordower JH (2009) Alterations in lysosomal and proteasomal markers in Parkinson’s disease: relationship to alpha-synuclein inclusions. Neurobiol Dis 35:385–398PubMedCrossRefGoogle Scholar
  51. 51.
    Masliah E, Rockenstein E, Veinbergs I, Mallory M, Hashimoto M, Takeda A, Sagara Y, Sisk A, Mucke L (2000) Dopaminergic loss and inclusion body formation in α-synuclein mice: implications for neurodegenerative disorders. Science 287:1265–1269PubMedCrossRefGoogle Scholar
  52. 52.
    Hashimoto M, Hsu LJ, Xia Y, Takeda A, Sisk A, Sundsmo M, Masliah E (1999) Oxidative stress induces amyloid-like aggregate formation of NACP/α-synuclein in vitro. Neuroreport 10:717–721PubMedCrossRefGoogle Scholar
  53. 53.
    Jungmann J, Reins HA, Schobert C, Jentsch S (1993) Resistance to cadmium mediated by ubiquitin-dependent proteolysis. Nature 361:369–371PubMedCrossRefGoogle Scholar
  54. 54.
    McNaught KS, Björklund LM, Belizaire R, Isacson O, Jenner P, Olanow CW (2002) Proteasome inhibition causes nigral degeneration with inclusion bodies in rats. Neuroreport 13:1437–1441PubMedCrossRefGoogle Scholar
  55. 55.
    Larsen CN, Krantz BA, Wilkinson KD (1998) Substrate specificity of deubiquitinating enzymes: ubiquitin C-terminal hydrolases. Biochemistry 37:3358–3368PubMedCrossRefGoogle Scholar
  56. 56.
    Giasson BI, Lee VM (2001) Parkin and the molecular pathways of Parkinson’s disease. Neuron 31:885–888PubMedCrossRefGoogle Scholar
  57. 57.
    Leroy E, Boyer R, Auburger G, Leube B, Ulm G, Mezey E, Harta G, Brownstein MJ, Jonnalagada S, Chernova T, Dehejia A, Lavedan C, Gasser T, Steinbach PJ, Wilkinson KD, Polymeropoulos MH (1998) The ubiquitin pathway in Parkinson’s disease. Nature 395:451–452PubMedCrossRefGoogle Scholar
  58. 58.
    Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr (2002) The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson’s disease susceptibility. Cell 111:209–218PubMedCrossRefGoogle Scholar
  59. 59.
    Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608PubMedCrossRefGoogle Scholar
  60. 60.
    von Coelln R, Dawson VL, Dawson TM (2004) Parkin-associated Parkinson’s disease. Cell Tissue Res 318:175–184CrossRefGoogle Scholar
  61. 61.
    Naoi M, Maruyama W, Doster P, Kohda K, Kaiya T (1996) A novel enzyme enantio-selectively synthesizes (R)salsolinol, a precursor of a dopaminergic neurotoxin, N-methyl(R)salsolinol. Neurosci Lett 212:183–186PubMedCrossRefGoogle Scholar
  62. 62.
    Naoi M, Maruyama W, Akao Y, Yi H (2002) Dopamine-derived endogenous N-methyl-(R)-salsolinol: its role in Parkinson’s disease. Neurotoxicol Teratol 24:579–591PubMedCrossRefGoogle Scholar
  63. 63.
    Musshoff F, Schmidt P, Dettmeyer R, Priemer F, Wittig H, Madea B (1999) A systematic regional study of dopamine and dopamine-derived salsolinol and norsalsolinol levels in human brain areas. Forensic Sci Int 105:1–11PubMedCrossRefGoogle Scholar
  64. 64.
    Musshoff F, Schmidt P, Dettmeyer R, Primer F, Jachau K, Madea B (2000) Determination of dopamine and dopamine-derived (R)-/(S)-salsolinol and norsalsolinol in various human brain areas using solid-phase extraction and gas chromatography/mass spectrometry. Forensic Sci Int 113:359–366PubMedCrossRefGoogle Scholar
  65. 65.
    Toth BE, Homicsko K, Radnai B, Maruyama W, Demaria JE, Vecsernyes M, Fekete MIK, Fulop F, Naoi M, Freeman ME, Nagy GM (2001) Salsolinol is a putative endogenous neuro-intermediate lobe prolactin-releasing factor. J Neuroendocrinol 13:1042–1050PubMedCrossRefGoogle Scholar
  66. 66.
    Naoi M, Maruyama W, Nagy GM (2004) Dopamine-derived salsolinol derivatives as endogenous monoamine oxidase inhibitors: occurrence, metabolism and function in human brains. Neurotoxicol 25:193–204CrossRefGoogle Scholar
  67. 67.
    Storch A, Kaftan A, Burkhard K, Schwartz J (2000) 1-Methyl-6, 7-dihydroxy-1, 2, 3, 4-tetrahydroisoquinoline (salsolinol) is toxic to dopaminergic neuroblastoma SH-SY5Y cells via impairment of cellular energy metabolism. Brain Res 855:67–75PubMedCrossRefGoogle Scholar
  68. 68.
    Maruyama W, Abe T, Tohgi H, Dostert P, Naoi M (1996) A dopaminergic neurotoxin, (R)-N-methylsalsolinol increases in parkinsonian cerebrospinal fluid. Ann Neurol 40:119–122PubMedCrossRefGoogle Scholar
  69. 69.
    Surendran S, Kumaresan G (2007) Neurochemical changes and therapeutic approaches in Canavan disease. In: Surendran S (ed) Neurochemistry of metabolic diseases-lysosomal storage diseases, phenylketonuria and Canavan disease. Research Signpost, India, pp 119–132Google Scholar
  70. 70.
    Surendran S (2005) Canavan disease: genomic interaction and metabolic levels. EXCLI J 4:77–86Google Scholar
  71. 71.
    Surendran S, Matalon R, Tyring SK (2006) Upregulation of aspartoacylase activity in the duodenum of obesity induced diabetes mouse: implications on diabetic neuropathy. Biochem Biophys Res Commun 345:973–975PubMedCrossRefGoogle Scholar
  72. 72.
    Surendran S, Bamforth FJ, Chan A, Tyring SK, Goodman SI, Matalon R (2003) Mild elevation of N-acetylaspartic acid and macrocephaly: diagnostic problem. J Child Neurol 18:809–812PubMedCrossRefGoogle Scholar
  73. 73.
    Surendran S (2007) Upregulation of aspartoacylase seen in diabetes is due to advanced glycation end-products. Med Hypotheses 68:926PubMedCrossRefGoogle Scholar
  74. 74.
    Surendran S (2008) N-Acetyl aspartate induces nitric oxide to result neurodegeneration in Canavan disease. Biosci hypotheses 1:228–229CrossRefGoogle Scholar
  75. 75.
    Song YJ, Halliday GM, Holton JL, Lashley T, O’Sullivan SS, McCann H, Lees AJ, Ozawa T, Williams DR, Lockhart PJ, Revesz TR (2009) Degeneration in different parkinsonian syndromes relates to astrocyte type and astrocyte protein expression. J Neuropathol Exp Neurol 68:1073–1083PubMedCrossRefGoogle Scholar
  76. 76.
    Forno LS, DeLanney LE, Irwin I, Di Monte D, Langston JW (1992) Astrocytes and Parkinson’s disease. Prog Brain Res 94:429–436PubMedCrossRefGoogle Scholar
  77. 77.
    Khan SA, Priyamvada S, Farooq N, Khan S, Khan MW, Yusufi AN (2009) Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Pharmacol Res 59:254–262PubMedCrossRefGoogle Scholar
  78. 78.
    Guo Q, Zhao BL, Li MF, Shen SR, Xin WJ (1996) Studies on protective mechanisms of four components of green tea polyphenols (GTP) against lipid peroxidation in synaptosomes. Biochim Biophys Acta 1304:210–222PubMedGoogle Scholar
  79. 79.
    Guo Q, Zhao BL, Hou JW, Xin WJ (1999) ESR study on the structure-antioxidant activity relationship of tea catechins and their epimers. Biochim Biophys Acta 1427:13–23PubMedGoogle Scholar
  80. 80.
    Zhao BL, Guo Q, Xin WJ (2001) Free radical scavenging by green tea polyphenols. Methods Enzymol 335:217–231PubMedCrossRefGoogle Scholar
  81. 81.
    Nie GJ, Wei TT, Zhao BL (2001) Polyphenol protection of DNA against damage. Methods Enzymol 335:232–244PubMedCrossRefGoogle Scholar
  82. 82.
    Inanami O, Watanabe Y, Syuto B, Nakano M, Tsuji M, Kuwabara M (1998) Oral administration of (-) catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil. Free Radic Res 29:359–365PubMedCrossRefGoogle Scholar
  83. 83.
    Yoneda T, Hiramatsu M, Skamoto N, Togasaki K, Komatsu M, Yamaguchi K (1995) Antioxidant effects of ‘‘b catechin’’. Biochem Mol Biol Int 35:995–1008PubMedGoogle Scholar
  84. 84.
    Kurzer MS, Xu X (1997) Dietary phytoestrogens. Annu Rev Nutr 17:353–381PubMedCrossRefGoogle Scholar
  85. 85.
    Chan WH, Yu JS (2000) Inhibition of UV irradiation-induced oxidative stress and apoptotic biochemical changes in human epidermal carcinoma A431 cells by genistein. J Cell Biochem 78:73–84PubMedCrossRefGoogle Scholar
  86. 86.
    Johnson KL, Vaillant F, Lawen A (1996) Protein tyrosine kinase inhibitors prevent didemnin B-induced apoptosis in HL-60 cells. FEBS Lett 383:1–5PubMedCrossRefGoogle Scholar
  87. 87.
    Choi JY, Park CS, Kim DJ, Cho MH, Jin BK, Pie JE, Chung WG (2002) Prevention of nitric oxide-mediated 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-induced Parkinson’s disease in mice by tea phenolic epigallocatechin 3-gallate. Neurotoxicology 23:367–374PubMedCrossRefGoogle Scholar
  88. 88.
    Schulz JB, Matthews RT, Muquit MM, Browne SE, Beal MF (1995) Inhibition of neuronal nitric oxide synthase by 7-nitroindazole protects against MPTP-induced neurotoxicity in mice. J Neurochem 64:936–939PubMedCrossRefGoogle Scholar
  89. 89.
    Hantraye P, Brouillet E, Ferrante R, Palfi S, Dolan R, Matthews RT, Beal MF (1996) Inhibition of neuronal nitric oxide synthase prevents MPTP-induced parkinsonism in baboons. Nat Med 2:1017–1021PubMedCrossRefGoogle Scholar
  90. 90.
    Masci A, Mastronicola D, Arese M, Piane M, De Amicis A, Blanck TJ, Chessa L, Sarti P (2008) Control of cell respiration by nitric oxide in ataxia telangiectasia lymphoblastoid cells. Biochim Biophys Acta 1777:66–73PubMedCrossRefGoogle Scholar
  91. 91.
    Shults CW, Beal MF, Fontaine D, Nakano K, Haas RH (1998) Absorption, tolerability, and effects on mitochondrial activity of oral coenzyme Q10 in parkinsonian patients. Neurology 50:793–795PubMedGoogle Scholar
  92. 92.
    Beal MF, Matthews RT, Tieleman A, Shults CW (1998) Coenzyme Q10 attenuates the 1-methyl-4-phenyl-1, 2, 3, tetrahydropyridine (MPTP) induced loss of striatal dopamine and dopaminergic axons in aged mice. Brain Res 783:109–114PubMedCrossRefGoogle Scholar
  93. 93.
    Ridet JL, Bensadoun JC, Deglon N, Aebischer P, Zurn AD (2006) Lentivirus-mediated expression of glutathione peroxidase: neuroprotection in murine models of Parkinson’s disease. Neurobiol Dis 21:29–34PubMedCrossRefGoogle Scholar
  94. 94.
    Thiruchelvam M, Prokopenko O, Cory-Slechta DA, Richfield EK, Buckley B, Mirochnitchenko O (2005) Overexpression of superoxide dismutase or glutathione peroxidase protects against the paraquat + maneb-induced Parkinson disease phenotype. J Biol Chem 280:22530–22539PubMedCrossRefGoogle Scholar
  95. 95.
    Shoulson I (1998) DATATOP: a decade of neuroprotective inquiry. Parkinson Study Group. Deprenyl and tocopherol antioxidative therapy of parkinsonism. Ann Neurol 44:S160–S166PubMedGoogle Scholar
  96. 96.
    McCarthy S, Somayajulu M, Sikorska M, Borowy-Borowski H, Pandey S (2004) Paraquat induces oxidative stress and neuronal cell death; neuroprotection by water-soluble coenzyme Q10. Toxicol Appl Pharmacol 201:21–31PubMedCrossRefGoogle Scholar
  97. 97.
    Horvath TL, Diano S, Leranth C, Garcia-Segura LM, Cowley MA, Shanabrough M, Elsworth JD, Sotonyi P, Roth RH, Dietrich EH, Matthews RT, Barnstable CJ, Redmond DE Jr (2003) Coenzyme Q induces nigral mitochondrial uncoupling and prevents nigral cell loss in a primate model of Parkinson’s disease. Endocrinology 144:2757–2760PubMedCrossRefGoogle Scholar
  98. 98.
    Shults CW, Oakes D, Kieburtz K, Beal MF, Haas R, Plumb S, Juncos JL et al (2002) Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol 59:1541–1550PubMedCrossRefGoogle Scholar
  99. 99.
    Klivenyi P, Siwek D, Gardian G, Yang L, Starkov A, Cleren C, Ferrante RJ, Kowall NW, Abeliovich A, Beal MF (2006) Mice lacking alpha-synuclein are resistant to mitochondrial toxins. Neurobiol Dis 21:541–548PubMedCrossRefGoogle Scholar
  100. 100.
    Parkinson Study Group (2004) A controlled, randomized, delayed-start study of rasagiline in early Parkinson disease. Arch Neurol 61:561–566CrossRefGoogle Scholar
  101. 101.
    Chen H, Zhang SM, Hernan MA, Schwarzschild MA, Willett WC, Colditz GA, Speizer FE, Ascherio A (2003) Nonsteroidal anti-inflammatory drugs and the risk of Parkinson disease. Arch Neurol 60:1059–1064PubMedCrossRefGoogle Scholar
  102. 102.
    Lagouge M, Argmann C, Gerhart-Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J et al (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127:1109–1122PubMedCrossRefGoogle Scholar
  103. 103.
    Lu KT, Ko MC, Chen BY, Huang JC, Hsieh CW, Lee MC, Chiou RY, Wung BS, Peng CH, Yang YL (2008) Neuroprotective effects of resveratrol on MPTP-induced neuron loss mediated by free radical scavenging. J Agric Food Chem 56:6910–6913PubMedCrossRefGoogle Scholar
  104. 104.
    Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, Olanow CW et al (2004) Levodopa and the progression of Parkinson’s disease. N Engl J Med 351:2498–2508PubMedCrossRefGoogle Scholar
  105. 105.
    Hely MA, Reid WG, Adena MA, Haliday GM, Morris JG (2008) The Sydney multicenter study of Parkinson’s disease: the inevitability of dementia at 20 years. Mov Disord 23:837–844PubMedCrossRefGoogle Scholar
  106. 106.
    Rascol O, Goetz C, Koller W, Poewe W, Sampaio C (2002) Treatment interventions for Parkinson’s disease: an evidence based assessment. Lancet 359:1589–1598PubMedCrossRefGoogle Scholar
  107. 107.
    Grosset D (2008) Dopamine agonists and therapy compliance. Neurol Sci 29:S375–S376PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.School of MedicineLSUHSCNew OrleansUSA
  2. 2.Department of AnatomyMelmaruvathur Adhi Parasakthi Institute of Medical SciencesMelmaruvathurIndia

Personalised recommendations