Journal of Neural Transmission

, Volume 119, Issue 8, pp 891–910 | Cite as

Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases

  • Mahesh Ramalingam
  • Sung-Jin KimEmail author
Basic Neurosciences, Genetics and Immunology - Review article


The continuous production and efflux of reactive oxygen/nitrogen species from endogenous and exogenous sources can damage biological molecules and initiate a cascade of events. Mitochondria are pivotal in controlling cell survival and death. Cumulative oxidative stress, disrupted mitochondrial respiration, and mitochondrial damage are related with various neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and others. Biochemical cascades of apoptosis are mediated in signaling molecules, including protein kinases and transcription factors. The expressions in the pro-apoptotic signal transduction networks may indeed promote cell death and degeneration in brain cells. The regulation of that protein phosphorylation by kinases and phosphatases is emerging as a prerequisite mechanism in the control of the apoptotic cell death program. In this review, we attempt to put forth the evidence for possible mechanistic explanations for involvement of free radicals in the pathogenesis of neurodegenerative diseases.


Free radicals Neurons Apoptosis Necrosis Signaling Neurodegeneration 



This work was supported by a post-doctoral fellowship grant from the Kyung Hee University in 2011 (KHU-20110696).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abe-Dohmae S, Harada N, Yamada K, Tanaka R (1993) Bcl-2 gene is highly expressed during neurogenesis in the central nervous system. Biochem Biophys Res Commun 191(3):915–921. doi: S0006291X83713045[pii] PubMedCrossRefGoogle Scholar
  2. Allsopp TE, Wyatt S, Paterson HF, Davies AM (1993) The proto-oncogene bcl-2 can selectively rescue neurotrophic factor-dependent neurons from apoptosis. Cell 73(2):295–307PubMedCrossRefGoogle Scholar
  3. Andreassen OA, Ferrante RJ, Dedeoglu A, Albers DW, Klivenyi P, Carlson EJ, Epstein CJ, Beal MF (2001) Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp Neurol 167(1):189–195. doi: 10.1006/exnr.2000.7525 PubMedCrossRefGoogle Scholar
  4. Andreyev AY, Kushnareva YE, Starkov AA (2005) Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 70(2):200–214CrossRefGoogle Scholar
  5. Bae BI, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y, Hayward SD, Moran TH, Montell C, Ross CA, Snyder SH, Sawa A (2005) p53 mediates cellular dysfunction and behavioral abnormalities in Huntington’s disease. Neuron 47(1):29–41. doi: 10.1016/j.neuron.2005.06.005 PubMedCrossRefGoogle Scholar
  6. Baeuerle PA, Baltimore D (1996) NF-kappa B: ten years after. Cell 87(1):13–20PubMedCrossRefGoogle Scholar
  7. Bamford KA, Caine ED, Kido DK, Cox C, Shoulson I (1995) A prospective evaluation of cognitive decline in early Huntington’s disease: functional and radiographic correlates. Neurology 45(10):1867–1873PubMedCrossRefGoogle Scholar
  8. Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7(1):111–118. doi: 10.1002/glia.440070117 PubMedCrossRefGoogle Scholar
  9. Bannai S, Ishii T (1982) Transport of cystine and cysteine and cell growth in cultured human diploid fibroblasts: effect of glutamate and homocysteate. J Cell Physiol 112(2):265–272. doi: 10.1002/jcp.1041120216 PubMedCrossRefGoogle Scholar
  10. Beal MF (1992) Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses? Ann Neurol 31(2):119–130. doi: 10.1002/ana.410310202 PubMedCrossRefGoogle Scholar
  11. Beal MF (1996) Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol 6(5):661–666PubMedCrossRefGoogle Scholar
  12. Beal MF (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci 23(7):298–304PubMedCrossRefGoogle Scholar
  13. Beal MF, Ferrante RJ, Browne SE, Matthews RT, Kowall NW, Brown RH Jr (1997) Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann Neurol 42(4):644–654. doi: 10.1002/ana.410420416 PubMedCrossRefGoogle Scholar
  14. Becker T, Gebert M, Pfanner N, van der Laan M (2009) Biogenesis of mitochondrial membrane proteins. Curr Opin Cell Biol 21(4):484–493. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  15. Beckman JS (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9(5):836–844. doi: 10.1021/tx9501445 PubMedCrossRefGoogle Scholar
  16. Behl C, Davis J, Cole GM, Schubert D (1992) Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem Biophys Res Commun 186(2):944–950PubMedCrossRefGoogle Scholar
  17. Benard G, Faustin B, Passerieux E, Galinier A, Rocher C, Bellance N, Delage JP, Casteilla L, Letellier T, Rossignol R (2006) Physiological diversity of mitochondrial oxidative phosphorylation. Am J Physiol Cell Physiol 291(6):C1172–C1182. doi: 10.1152/ajpcell.00195.2006 PubMedCrossRefGoogle Scholar
  18. Benedetti A, Comporti M, Esterbauer H (1980) Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim Biophys Acta 620(2):281–296PubMedCrossRefGoogle Scholar
  19. Bergeron C (1995) Oxidative stress: its role in the pathogenesis of amyotrophic lateral sclerosis. J Neurol Sci 129(Suppl):81–84PubMedCrossRefGoogle Scholar
  20. Bjelland S, Seeberg E (2003) Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat Res 531(1–2):37–80PubMedGoogle Scholar
  21. Bolanos JP, Heales SJ, Peuchen S, Barker JE, Land JM, Clark JB (1996) Nitric oxide-mediated mitochondrial damage: a potential neuroprotective role for glutathione. Free Radic Biol Med 21(7):995–1001PubMedCrossRefGoogle Scholar
  22. Bolokadze N, Lobjanidze I, Momtselidze N, Solomonia R, Shakarishvili R, McHedlishvili G (2004) Blood rheological properties and lipid peroxidation in cerebral and systemic circulation of neurocritical patients. Clin Hemorheol Microcirc 30(2):99–105PubMedGoogle Scholar
  23. Bowling AC, Schulz JB, Brown RH Jr, Beal MF (1993) Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem 61(6):2322–2325PubMedCrossRefGoogle Scholar
  24. Brigelius-Flohe R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27(9–10):951–965PubMedCrossRefGoogle Scholar
  25. Browne SE, Ferrante RJ, Beal MF (1999) Oxidative stress in Huntington’s disease. Brain Pathol 9(1):147–163PubMedCrossRefGoogle Scholar
  26. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96(6):857–868PubMedCrossRefGoogle Scholar
  27. Brunk UT, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33(5):611–619PubMedCrossRefGoogle Scholar
  28. Burke RE (1999) Parkinson’s disease. In: Koliatsos VE, Ratan RR (eds) Cell death and diseases of the nervous system. Humana Press, Totowa, pp 459–475CrossRefGoogle Scholar
  29. Butterfield DA, Kanski J (2001) Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev 122(9):945–962PubMedCrossRefGoogle Scholar
  30. Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15(1):7–10PubMedCrossRefGoogle Scholar
  31. Chalovich EM, Zhu JH, Caltagarone J, Bowser R, Chu CT (2006) Functional repression of cAMP response element in 6-hydroxydopamine-treated neuronal cells. J Biol Chem 281(26):17870–17881. doi: 10.1074/jbc.M602632200 PubMedCrossRefGoogle Scholar
  32. Chan PH (2004) Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res 29(11):1943–1949PubMedCrossRefGoogle Scholar
  33. Chang J, Siedlak S, Moreira P, Nunomura A, Castellani RJ, Smith MA, Zhu X, Perry G, Casadesus G (2011) Oxidative stress in Alzheimer’s disease: a critical appraisal of the causes and the consequences. In: Basu S, Wiklund L (eds) Studies on experimental models. Oxidative stress in applied basic research and clinical practice. Humana Press, Totowa, pp 211–220. doi: 10.1007/978-1-60761-956-7_9
  34. Chen J, Nagayama T, Jin K, Stetler RA, Zhu RL, Graham SH, Simon RP (1998) Induction of caspase-3-like protease may mediate delayed neuronal death in the hippocampus after transient cerebral ischemia. J Neurosci 18(13):4914–4928PubMedGoogle Scholar
  35. Chu CT, Berman SB (2011) Mitochondrial fission-fusion and Parkinson’s disease: a dynamic question of compensatory networks. In: Lu B (ed) Mitochondrial dynamics and neurodegeneration. Springer, Netherlands, pp 197–213. doi: 10.1007/978-94-007-1291-1_7
  36. Coles B, Ketterer B (1990) The role of glutathione and glutathione transferases in chemical carcinogenesis. Crit Rev Biochem Mol Biol 25(1):47–70. doi: 10.3109/10409239009090605 PubMedCrossRefGoogle Scholar
  37. Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262(5134):689–695PubMedCrossRefGoogle Scholar
  38. Cui J, Holmes EH, Greene TG, Liu PK (2000) Oxidative DNA damage precedes DNA fragmentation after experimental stroke in rat brain. FASEB J 14(7):955–967PubMedGoogle Scholar
  39. Culotta VC, Yang M, O’Halloran TV (2006) Activation of superoxide dismutases: putting the metal to the pedal. Biochim Biophys Acta 1763(7):747–758. doi: 10.1016/j.bbamcr.2006.05.003 PubMedCrossRefGoogle Scholar
  40. Dawson VL, Dawson TM (1996) Nitric oxide neurotoxicity. J Chem Neuroanat 10(3–4):179–190PubMedCrossRefGoogle Scholar
  41. de Belleroche J, Orrell R, King A (1995) Familial amyotrophic lateral sclerosis/motor neurone disease (FALS): a review of current developments. J Med Genet 32(11):841–847PubMedCrossRefGoogle Scholar
  42. Demirkaya S, Topcuoglu MA, Aydin A, Ulas UH, Isimer AI, Vural O (2001) Malondialdehyde, glutathione peroxidase and superoxide dismutase in peripheral blood erythrocytes of patients with acute cerebral ischemia. Eur J Neurol 8(1):43–51PubMedCrossRefGoogle Scholar
  43. Desagher S, Glowinski J, Premont J (1996) Astrocytes protect neurons from hydrogen peroxide toxicity. J Neurosci 16(8):2553–2562PubMedGoogle Scholar
  44. Deschamps V, Barberger-Gateau P, Peuchant E, Orgogozo JM (2001) Nutritional factors in cerebral aging and dementia: epidemiological arguments for a role of oxidative stress. Neuroepidemiology 20(1):7–15PubMedCrossRefGoogle Scholar
  45. Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267(16):4912–4916PubMedCrossRefGoogle Scholar
  46. Du H, Yan SS (2010) Mitochondrial medicine for neurodegenerative diseases. Int J Biochem Cell Biol 42(5):560–572. doi: 10.1016/j.biocel.2010.01.004 PubMedCrossRefGoogle Scholar
  47. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, Lipsky PE (1998) Cyclooxygenase in biology and disease. FASEB J 12(12):1063–1073PubMedGoogle Scholar
  48. Ebadi M, Srinivasan SK, Baxi MD (1996) Oxidative stress and antioxidant therapy in Parkinson’s disease. Prog Neurobiol 48(1):1–19PubMedCrossRefGoogle Scholar
  49. Eguchi Y, Shimizu S, Tsujimoto Y (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 57(10):1835–1840PubMedGoogle Scholar
  50. Emerit J, Edeas M, Bricaire F (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58(1):39–46PubMedCrossRefGoogle Scholar
  51. Endres M, Wang ZQ, Namura S, Waeber C, Moskowitz MA (1997) Ischemic brain injury is mediated by the activation of poly(ADP-ribose)polymerase. J Cereb Blood Flow Metab 17(11):1143–1151. doi: 10.1097/00004647-199711000-00002 PubMedCrossRefGoogle Scholar
  52. Enomoto A, Itoh K, Nagayoshi E, Haruta J, Kimura T, O’Connor T, Harada T, Yamamoto M (2001) High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. Toxicol Sci 59(1):169–177PubMedCrossRefGoogle Scholar
  53. Ferrante RJ, Browne SE, Shinobu LA, Bowling AC, Baik MJ, MacGarvey U, Kowall NW, Brown RH Jr, Beal MF (1997) Evidence of increased oxidative damage in both sporadic and familial amyotrophic lateral sclerosis. J Neurochem 69(5):2064–2074PubMedCrossRefGoogle Scholar
  54. Fields RD, Stevens-Graham B (2002) New insights into neuron-glia communication. Science 298(5593):556–562. doi: 10.1126/science.298.5593.556 PubMedCrossRefGoogle Scholar
  55. Finkelstein E, Rosen GM, Rauckman EJ (1980) Spin trapping of superoxide and hydroxyl radical: practical aspects. Arch Biochem Biophys 200(1):1–16PubMedCrossRefGoogle Scholar
  56. Florence TM (1992) The role of free radicals in cancer and aging. In: Dreosti IE (ed) Trace elements, micronutrients, and free radicals. Contemporary issues in biomedicine, ethics, and society. Humana Press, Totowa, pp 171–198. doi: 10.1007/978-1-4612-0419-0_8
  57. Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222(3):236–245PubMedCrossRefGoogle Scholar
  58. Floyd RA, Carney JM (1992) Free radical damage to protein and DNA: mechanisms involved and relevant observations on brain undergoing oxidative stress. Ann Neurol 32(Suppl):S22–S27PubMedCrossRefGoogle Scholar
  59. Floyd RA, West MS, Eneff KL, Schneider JE, Wong PK, Tingey DT, Hogsett WE (1990) Conditions influencing yield and analysis of 8-hydroxy-2’-deoxyguanosine in oxidatively damaged DNA. Anal Biochem 188(1):155–158PubMedCrossRefGoogle Scholar
  60. Fridovich I (1986) Superoxide dismutases. Adv Enzymol Relat Areas Mol Biol 58:61–97PubMedGoogle Scholar
  61. Friedman J (2011) The role of free radicals in the nervous system. In: Gadoth N, Göbel HH (eds) Oxidative stress and free radical damage in neurology. Oxidative stress in applied basic research and clinical practice, 1 edn. Humana Press, Totowa, pp 1–17. doi: 10.1007/978-1-60327-514-9_1
  62. Fujimura M, Morita-Fujimura Y, Murakami K, Kawase M, Chan PH (1998) Cytosolic redistribution of cytochrome c after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab 18(11):1239–1247. doi: 10.1097/00004647-199811000-00010 PubMedCrossRefGoogle Scholar
  63. Gabbita SP, Lovell MA, Markesbery WR (1998) Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J Neurochem 71(5):2034–2040PubMedCrossRefGoogle Scholar
  64. Giulian D, Li J, Li X, George J, Rutecki PA (1994) The impact of microglia-derived cytokines upon gliosis in the CNS. Dev Neurosci 16(3–4):128–136PubMedCrossRefGoogle Scholar
  65. Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426(6968):895–899. doi: 10.1038/nature02263 PubMedCrossRefGoogle Scholar
  66. Gorman AM, McGowan A, O’Neill C, Cotter T (1996) Oxidative stress and apoptosis in neurodegeneration. J Neurol Sci 139(Suppl):45–52PubMedCrossRefGoogle Scholar
  67. Gotz ME, Kunig G, Riederer P, Youdim MB (1994) Oxidative stress: free radical production in neural degeneration. Pharmacol Ther 63(1):37–122PubMedCrossRefGoogle Scholar
  68. Greenamyre JT (1986) The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 43(10):1058–1063PubMedCrossRefGoogle Scholar
  69. Grunewald T, Beal MF (1999) Bioenergetics in Huntington’s disease. Ann N Y Acad Sci 893:203–213PubMedCrossRefGoogle Scholar
  70. Guglielmo MA, Chan PT, Cortez S, Stopa EG, McMillan P, Johanson CE, Epstein M, Doberstein CE (1998) The temporal profile and morphologic features of neuronal death in human stroke resemble those observed in experimental forebrain ischemia: the potential role of apoptosis. Neurol Res 20(4):283–296PubMedGoogle Scholar
  71. Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59(5):1609–1623PubMedCrossRefGoogle Scholar
  72. Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97(6):1634–1658. doi: 10.1111/j.1471-4159.2006.03907.x PubMedCrossRefGoogle Scholar
  73. Halliwell B, Clement MV, Long LH (2000) Hydrogen peroxide in the human body. FEBS Lett 486(1):10–13PubMedCrossRefGoogle Scholar
  74. Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. Trends Neurosci 8:22–26. doi: 10.1016/0166-2236(85)90010-4 CrossRefGoogle Scholar
  75. Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine, 3rd edn. Oxford science publications, Clarendon Press, Oxford University Press, OxfordGoogle Scholar
  76. Han Y, Kim SJ (2003) Memory enhancing actions of Asiasari radix extracts via activation of insulin receptor and extracellular signal regulated kinase (ERK) I/II in rat hippocampus. Brain Res 974(1–2):193–201PubMedCrossRefGoogle Scholar
  77. Han Y, Kwon EH, Kim SJ (2003) Protection of brain cells against AMPA-induced damage by Asiasari Radix extracts. Phytother Res 17(8):882–886. doi: 10.1002/ptr.1176 PubMedCrossRefGoogle Scholar
  78. Hansson E, Ronnback L (2003) Glial neuronal signaling in the central nervous system. FASEB J 17(3):341–348. doi: 10.1096/fj.02-0429rev PubMedCrossRefGoogle Scholar
  79. Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069. doi: 10.1146/ PubMedCrossRefGoogle Scholar
  80. Hazen SL, Hsu FF, Gaut JP, Crowley JR, Heinecke JW (1999) Modification of proteins and lipids by myeloperoxidase. Methods Enzymol 300:88–105PubMedCrossRefGoogle Scholar
  81. Hazra TK, Hill JW, Izumi T, Mitra S (2001) Multiple DNA glycosylases for repair of 8-oxoguanine and their potential in vivo functions. Progr Nucleic Acid Res Mol Biol 68:193–205CrossRefGoogle Scholar
  82. Heales SJ, Bolanos JP, Land JM, Clark JB (1994) Trolox protects mitochondrial complex IV from nitric oxide-mediated damage in astrocytes. Brain Res 668(1–2):243–245PubMedCrossRefGoogle Scholar
  83. Hensley K, Maidt ML, Yu Z, Sang H, Markesbery WR, Floyd RA (1998) Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation. J Neurosci 18(20):8126–8132PubMedGoogle Scholar
  84. Higgins CM, Jung C, Ding H, Xu Z (2002) Mutant Cu, Zn superoxide dismutase that causes motoneuron degeneration is present in mitochondria in the CNS. J Neurosci 22(6):RC215PubMedGoogle Scholar
  85. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75(2):241–251PubMedCrossRefGoogle Scholar
  86. Hofman A, Grobbee DE, Jong PTVM, Ouweland FA (1991) Determinants of disease and disability in the elderly: The Rotterdam elderly study. Eur J Epidemiol 7(4):403–422. doi: 10.1007/bf00145007 PubMedCrossRefGoogle Scholar
  87. Hsu TC, Young MR, Cmarik J, Colburn NH (2000) Activator protein 1 (AP-1)- and nuclear factor kappaB (NF-kappaB)-dependent transcriptional events in carcinogenesis. Free Radic Biol Med 28(9):1338–1348PubMedCrossRefGoogle Scholar
  88. Hur GM, Ryu YS, Yun HY, Jeon BH, Kim YM, Seok JH, Lee JH (1999) Hepatic ischemia/reperfusion in rats induces iNOS gene transcription by activation of NF-kappaB. Biochem Biophys Res Commun 261(3):917–922. doi: 10.1006/bbrc.1999.1143 PubMedCrossRefGoogle Scholar
  89. Imlay JA (2003) Pathways of oxidative damage. Annu Rev Microbiol 57:395–418. doi: 10.1146/annurev.micro.57.030502.090938 PubMedCrossRefGoogle Scholar
  90. Ischiropoulos H, Beckman JS (2003) Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest 111(2):163–169. doi: 10.1172/JCI17638 PubMedGoogle Scholar
  91. Ito Y, Arakawa M, Ishige K, Fukuda H (1999) Comparative study of survival signal withdrawal- and 4-hydroxynonenal-induced cell death in cerebellar granule cells. Neurosci Res 35(4):321–327PubMedCrossRefGoogle Scholar
  92. Jackson-Lewis V, Tocilescu MA, DeVries R, Alessi DM, Przedborski S (2011) MPTP and oxidative stress: it’s complicated! In: Basu S, Wiklund L (eds) Studies on experimental models. Oxidative stress in applied basic research and clinical practice. Humana Press, Totowa, pp 187–209. doi: 10.1007/978-1-60761-956-7_8
  93. Jaeschke H (1995) Mechanisms of oxidant stress-induced acute tissue injury. Proc Soc Exp Biol Med 209(2):104–111PubMedGoogle Scholar
  94. Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47(6 Suppl 3):S161–S170PubMedCrossRefGoogle Scholar
  95. Jenner P, Olanow CW (1998) Understanding cell death in Parkinson’s disease. Ann Neurol 44(3 Suppl 1):S72–S84PubMedGoogle Scholar
  96. Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (2005) Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases. Cell 120(5):649–661. doi: 10.1016/j.cell.2004.12.041 PubMedCrossRefGoogle Scholar
  97. Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7(3):153–163PubMedCrossRefGoogle Scholar
  98. Kehrer JP, Lund LG (1994) Cellular reducing equivalents and oxidative stress. Free Radic Biol Med 17(1):65–75PubMedCrossRefGoogle Scholar
  99. Keller JN, Dimayuga E, Chen Q, Thorpe J, Gee J, Ding Q (2004) Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. Int J Biochem Cell Biol 36(12):2376–2391. doi: 10.1016/j.biocel.2004.05.003 PubMedCrossRefGoogle Scholar
  100. Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257PubMedCrossRefGoogle Scholar
  101. Kim SJ, Han Y (2005) Insulin inhibits AMPA-induced neuronal damage via stimulation of protein kinase B (Akt). J Neural Transm 112(2):179–191. doi: 10.1007/s00702-004-0163-6 PubMedCrossRefGoogle Scholar
  102. Kim SJ, Lee K (2008) Extracts of Liriopsis tuber protect AMPA induced brain damage and improve memory with the activation of insulin receptor and ERK I/II. Phytother Res 22(11):1450–1457. doi: 10.1002/ptr.2475 PubMedCrossRefGoogle Scholar
  103. Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Invest 111(6):785–793. doi: 10.1172/JCI18182 PubMedGoogle Scholar
  104. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD (1997) The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis. Science 275(5303):1132–1136PubMedCrossRefGoogle Scholar
  105. Kohen R, Gati I (2000) Skin low molecular weight antioxidants and their role in aging and in oxidative stress. Toxicology 148(2–3):149–157PubMedCrossRefGoogle Scholar
  106. Kohen R, Nyska A (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30(6):620–650PubMedCrossRefGoogle Scholar
  107. Kokoszka JE, Coskun P, Esposito LA, Wallace DC (2001) Increased mitochondrial oxidative stress in the Sod2 (+/−) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proc Natl Acad Sci USA 98(5):2278–2283. doi: 10.1073/pnas.051627098 PubMedCrossRefGoogle Scholar
  108. Koutsilieri E, Scheller C, Tribl F, Riederer P (2002) Degeneration of neuronal cells due to oxidative stress–microglial contribution. Parkinsonism Relat Disord 8(6):401–406PubMedCrossRefGoogle Scholar
  109. Kruman II, Wersto RP, Cardozo-Pelaez F, Smilenov L, Chan SL, Chrest FJ, Emokpae R Jr, Gorospe M, Mattson MP (2004) Cell cycle activation linked to neuronal cell death initiated by DNA damage. Neuron 41(4):549–561PubMedCrossRefGoogle Scholar
  110. Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219(4587):979–980PubMedCrossRefGoogle Scholar
  111. Lehtinen MK, Bonni A (2006) Modeling oxidative stress in the central nervous system. Curr Mol Med 6(8):871–881PubMedCrossRefGoogle Scholar
  112. Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P (1997) Intracellular adenosine triphosphate (ATP) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med 185(8):1481–1486PubMedCrossRefGoogle Scholar
  113. Lennon SV, Martin SJ, Cotter TG (1991) Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli. Cell Prolif 24(2):203–214PubMedCrossRefGoogle Scholar
  114. Levine RL, Wehr N, Williams JA, Stadtman ER, Shacter E (2000) Determination of carbonyl groups in oxidized proteins. Methods Mol Biol 99:15–24. doi: 10.1385/1-59259-054-3:15 PubMedGoogle Scholar
  115. Lewen A, Matz P, Chan PH (2000) Free radical pathways in CNS injury. J Neurotrauma 17(10):871–890PubMedCrossRefGoogle Scholar
  116. Li JJ, Rhim JS, Schlegel R, Vousden KH, Colburn NH (1998) Expression of dominant negative Jun inhibits elevated AP-1 and NF-kappaB transactivation and suppresses anchorage independent growth of HPV immortalized human keratinocytes. Oncogene 16(21):2711–2721. doi: 10.1038/sj.onc.1201798 PubMedCrossRefGoogle Scholar
  117. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X (1997) Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell 91(4):479–489PubMedCrossRefGoogle Scholar
  118. Liang LP, Patel M (2004) Iron-sulfur enzyme mediated mitochondrial superoxide toxicity in experimental Parkinson’s disease. J Neurochem 90(5):1076–1084. doi: 10.1111/j.1471-4159.2004.02567.x PubMedCrossRefGoogle Scholar
  119. Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795. doi: 10.1038/nature05292 PubMedCrossRefGoogle Scholar
  120. Lindenau J, Noack H, Possel H, Asayama K, Wolf G (2000) Cellular distribution of superoxide dismutases in the rat CNS. Glia 29(1):25–34. doi: 10.1002/(SICI)1098-1136(20000101)29:1<25:AID-GLIA3>3.0.CO;2-G PubMedCrossRefGoogle Scholar
  121. Liu D, Yang R, Yan X, McAdoo DJ (1994) Hydroxyl radicals generated in vivo kill neurons in the rat spinal cord: electrophysiological, histological, and neurochemical results. J Neurochem 62(1):37–44PubMedCrossRefGoogle Scholar
  122. Love S, Barber R, Wilcock GK (1998) Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man. Neuroreport 9(6):955–959PubMedCrossRefGoogle Scholar
  123. Lovell MA, Gabbita SP, Markesbery WR (1999) Increased DNA oxidation and decreased levels of repair products in Alzheimer’s disease ventricular CSF. J Neurochem 72(2):771–776PubMedCrossRefGoogle Scholar
  124. Macmillan-Crow LA, Cruthirds DL (2001) Invited review: manganese superoxide dismutase in disease. Free Radic Res 34(4):325–336PubMedCrossRefGoogle Scholar
  125. Mahesh R, Kim SJ (2009) The Protective effects of insulin on hydrogen peroxide-induced oxidative stress in C6 glial cells. Biomol Ther 17(4):395–402. doi: 10.4062/biomolther.2009.17.4.395 CrossRefGoogle Scholar
  126. Margaill I, Plotkine M, Lerouet D (2005) Antioxidant strategies in the treatment of stroke. Free Radic Biol Med 39(4):429–443. doi: 10.1016/j.freeradbiomed.2005.05.003 PubMedCrossRefGoogle Scholar
  127. Mariani E, Polidori MC, Cherubini A, Mecocci P (2005) Oxidative stress in brain aging, neurodegenerative and vascular diseases: an overview. J Chromatogr B Analyt Technol Biomed Life Sci 827(1):65–75. doi: 10.1016/j.jchromb.2005.04.023 PubMedCrossRefGoogle Scholar
  128. Mattson MP (2004) Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann N Y Acad Sci 1012:37–50PubMedCrossRefGoogle Scholar
  129. Mattson MP, Duan W, Pedersen WA, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6(1–2):69–81PubMedCrossRefGoogle Scholar
  130. Mattson MP, Pedersen WA, Duan W, Culmsee C, Camandola S (1999) Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer’s and Parkinson’s diseases. Ann N Y Acad Sci 893:154–175PubMedCrossRefGoogle Scholar
  131. McConkey DJ (1998) Biochemical determinants of apoptosis and necrosis. Toxicol Lett 99(3):157–168PubMedCrossRefGoogle Scholar
  132. Meister A (1992) On the antioxidant effects of ascorbic acid and glutathione. Biochem Pharmacol 44(10):1905–1915PubMedCrossRefGoogle Scholar
  133. Meister A (1995) Glutathione metabolism. Methods Enzymol 251:3–7PubMedCrossRefGoogle Scholar
  134. Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760. doi: 10.1146/ PubMedCrossRefGoogle Scholar
  135. Michikawa M, Lim KT, McLarnon JG, Kim SU (1994) Oxygen radical-induced neurotoxicity in spinal cord neuron cultures. J Neurosci Res 37(1):62–70. doi: 10.1002/jnr.490370109 PubMedCrossRefGoogle Scholar
  136. Mielke K, Herdegen T (2000) JNK and p38 stresskinases—degenerative effectors of signal-transduction-cascades in the nervous system. Prog Neurobiol 61(1):45–60. doi: S0301-0082(99)00042-8[pii] PubMedCrossRefGoogle Scholar
  137. 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(3):1450–1455PubMedCrossRefGoogle Scholar
  138. Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329(27):2002–2012. doi: 10.1056/NEJM199312303292706 PubMedCrossRefGoogle Scholar
  139. Moncada S, Palmer RM, Higgs EA (1989) Biosynthesis of nitric oxide from l-arginine. A pathway for the regulation of cell function and communication. Biochem Pharmacol 38(11):1709–1715PubMedCrossRefGoogle Scholar
  140. Morel Y, Barouki R (1999) Repression of gene expression by oxidative stress. Biochem J 342(Pt 3):481–496PubMedCrossRefGoogle Scholar
  141. Morrow JD (2005) Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans. Arterioscler Thromb Vasc Biol 25(2):279–286. doi: 10.1161/01.ATV.0000152605.64964.c0 PubMedCrossRefGoogle Scholar
  142. Mufson EJ, Kordower JH (1998) Nerve growth factor and its receptors in the primate forebrain: Alterations in Alzheimer’s disease and potential use in experimental therapeutics. In: Mattson MP (ed) Neuroprotective signal transduction. Humana Press, Totowa, pp 23–59Google Scholar
  143. Murakami K, Kondo T, Kawase M, Li Y, Sato S, Chen SF, Chan PH (1998) Mitochondrial susceptibility to oxidative stress exacerbates cerebral infarction that follows permanent focal cerebral ischemia in mutant mice with manganese superoxide dismutase deficiency. J Neurosci 18(1):205–213PubMedGoogle Scholar
  144. Murphy AN, Fiskum G, Beal MF (1999) Mitochondria in neurodegeneration: bioenergetic function in cell life and death. J Cereb Blood Flow Metab 19(3):231–245. doi: 10.1097/00004647-199903000-00001 PubMedCrossRefGoogle Scholar
  145. Nakamura T, Cho D-H, Lipton SA (2011) Role of the mitochondrial fission protein Drp1 in synaptic damage and neurodegeneration. In: Lu B (ed) Mitochondrial dynamics and neurodegeneration. Springer, Netherlands, pp 215–234. doi: 10.1007/978-94-007-1291-1_8
  146. Namura S, Zhu J, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J, Moskowitz MA (1998) Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci 18(10):3659–3668PubMedGoogle Scholar
  147. Naoi M, Dostert P, Yoshida M, Nagatsu T (1993) N-methylated tetrahydroisoquinolines as dopaminergic neurotoxins. Adv Neurol 60:212–217PubMedGoogle Scholar
  148. Niizuma K, Endo H, Chan PH (2009) Oxidative stress and mitochondrial dysfunction as determinants of ischemic neuronal death and survival. J Neurochem 109(Suppl 1):133–138. doi: 10.1111/j.1471-4159.2009.05897.x PubMedCrossRefGoogle Scholar
  149. Niki E, Saito T, Kawakami A, Kamiya Y (1984) Inhibition of oxidation of methyl linoleate in solution by vitamin E and vitamin C. J Biol Chem 259(7):4177–4182PubMedGoogle Scholar
  150. Nunomura A, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60(8):759–767PubMedGoogle Scholar
  151. O’Neill GP, Ford-Hutchinson AW (1993) Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 330(2):156–160PubMedGoogle Scholar
  152. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358PubMedCrossRefGoogle Scholar
  153. Olanow CW (1992) An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 32(Suppl):S2–S9PubMedCrossRefGoogle Scholar
  154. Olanow CW (1993) A radical hypothesis for neurodegeneration. Trends Neurosci 16(11):439–444PubMedCrossRefGoogle Scholar
  155. Olney JW (1989) Excitatory amino acids and neuropsychiatric disorders. Biol Psychiatry 26(5):505–525PubMedCrossRefGoogle Scholar
  156. Ong WY, Halliwell B (2004) Iron, atherosclerosis, and neurodegeneration: a key role for cholesterol in promoting iron-dependent oxidative damage? Ann N Y Acad Sci 1012:51–64PubMedCrossRefGoogle Scholar
  157. Onorato JM, Thorpe SR, Baynes JW (1998) Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging and disease. Ann N Y Acad Sci 854:277–290PubMedCrossRefGoogle Scholar
  158. Orrenius S, McConkey DJ, Bellomo G, Nicotera P (1989) Role of Ca2+ in toxic cell killing. Trends Pharmacol Sci 10(7):281–285PubMedCrossRefGoogle Scholar
  159. Palmieri B, Sblendorio V (2007) Oxidative stress tests: overview on reliability and use. Part I. Eur Rev Med Pharmacol Sci 11(5):309–342PubMedGoogle Scholar
  160. Panov AV, Gutekunst CA, Leavitt BR, Hayden MR, Burke JR, Strittmatter WJ, Greenamyre JT (2002) Early mitochondrial calcium defects in Huntington’s disease are a direct effect of polyglutamines. Nat Neurosci 5(8):731–736. doi: 10.1038/nn884 PubMedGoogle Scholar
  161. Patockova J, Marhol P, Tumova E, Krsiak M, Rokyta R, Stipek S, Crkovska J, Andel M (2003) Oxidative stress in the brain tissue of laboratory mice with acute post insulin hypoglycemia. Physiol Res 52(1):131–135PubMedGoogle Scholar
  162. Perry TL, Hansen S (1990) What excitotoxin kills striatal neurons in Huntington’s disease? Clues from neurochemical studies. Neurology 40(1):20–24PubMedCrossRefGoogle Scholar
  163. Peuchen S, Bolaños JP, Heales SJR, Almeida A, Duchen MR, Clark JB (1997) Interrelationships between astrocyte function, oxidative stress and antioxidant status within the central nervous system. Progr Neurobiol 52(4):261–281. doi: 10.1016/s0301-0082(97)00010-5 CrossRefGoogle Scholar
  164. Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 7(5):695–702PubMedCrossRefGoogle Scholar
  165. Polidori MC, Mecocci P, Browne SE, Senin U, Beal MF (1999) Oxidative damage to mitochondrial DNA in Huntington’s disease parietal cortex. Neurosci Lett 272(1):53–56PubMedCrossRefGoogle Scholar
  166. Poon HF, Calabrese V, Scapagnini G, Butterfield DA (2004) Free radicals: key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol A Biol Sci Med Sci 59(5):478–493PubMedCrossRefGoogle Scholar
  167. Raingeaud J, Gupta S, Rogers JS, Dickens M, Han J, Ulevitch RJ, Davis RJ (1995) Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J Biol Chem 270(13):7420–7426PubMedCrossRefGoogle Scholar
  168. Rao AV, Balachandran B (2002) Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci 5(5):291–309PubMedCrossRefGoogle Scholar
  169. Reed DJ, Savage MK (1995) Influence of metabolic inhibitors on mitochondrial permeability transition and glutathione status. Biochim Biophys Acta 1271(1):43–50PubMedCrossRefGoogle Scholar
  170. Reynolds A, Laurie C, Mosley RL, Gendelman HE (2007) Oxidative stress and the pathogenesis of neurodegenerative disorders. Int Rev Neurobiol 82:297–325. doi: 10.1016/S0074-7742(07)82016-2 PubMedCrossRefGoogle Scholar
  171. Richter C (1993) Pro-oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis. FEBS Lett 325(1–2):104–107PubMedCrossRefGoogle Scholar
  172. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A, Donaldson D, Goto J, O’Regan JP, Deng HX et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362(6415):59–62. doi: 10.1038/362059a0 PubMedCrossRefGoogle Scholar
  173. Sagara Y, Dargusch R, Chambers D, Davis J, Schubert D, Maher P (1998) Cellular mechanisms of resistance to chronic oxidative stress. Free Radic Biol Med 24(9):1375–1389PubMedCrossRefGoogle Scholar
  174. Saito A, Maier CM, Narasimhan P, Nishi T, Song YS, Yu F, Liu J, Lee YS, Nito C, Kamada H, Dodd RL, Hsieh LB, Hassid B, Kim EE, Gonzalez M, Chan PH (2005) Oxidative stress and neuronal death/survival signaling in cerebral ischemia. Mol Neurobiol 31(1–3):105–116. doi: 10.1385/MN:31:1-3:105 PubMedCrossRefGoogle Scholar
  175. Salvemini D, Settle SL, Masferrer JL, Seibert K, Currie MG, Needleman P (1995) Regulation of prostaglandin production by nitric oxide; an in vivo analysis. Br J Pharmacol 114(6):1171–1178PubMedGoogle Scholar
  176. Sayre LM, Perry G, Harris PL, Liu Y, Schubert KA, Smith MA (2000) In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer’s disease: a central role for bound transition metals. J Neurochem 74(1):270–279PubMedCrossRefGoogle Scholar
  177. Sayre LM, Perry G, Smith MA (1999) In situ methods for detection and localization of markers of oxidative stress: application in neurodegenerative disorders. Methods Enzymol 309:133–152PubMedCrossRefGoogle Scholar
  178. Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21(1):172–188. doi: 10.1021/tx700210j PubMedCrossRefGoogle Scholar
  179. Scandalios JG (2002) Oxidative stress responses—what have genome-scale studies taught us? Genome Biol 3(7):REVIEWS1019Google Scholar
  180. Schapira AH, Gu M, Taanman JW, Tabrizi SJ, Seaton T, Cleeter M, Cooper JM (1998) Mitochondria in the etiology and pathogenesis of Parkinson’s disease. Ann Neurol 44(3 Suppl 1):S89–S98PubMedGoogle Scholar
  181. Schwarcz R, Okuno E, White RJ, Bird ED, Whetsell WO Jr (1988) 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. Proc Natl Acad Sci USA 85(11):4079–4081PubMedCrossRefGoogle Scholar
  182. Siebenlist U, Franzoso G, Brown K (1994) Structure, regulation and function of NF-kappa B. Annu Rev Cell Biol 10:405–455. doi: 10.1146/annurev.cb.10.110194.002201 PubMedCrossRefGoogle Scholar
  183. Sies H (1985) Oxidative stress: introductory remarks. In: Sies H (ed) Oxidative stress. Academic Press, Orlando, pp 1–8Google Scholar
  184. Sies H (1986) Biochemistry of oxidative stress. Angew Chem 25(12):1058–1071. doi: 10.1002/anie.198610581 CrossRefGoogle Scholar
  185. Siman-Tov T, Gadoth N (2011) Free radicals in epilepsy. In: Gadoth N, Göbel HH (eds) Oxidative stress and free radical damage in neurology. Oxidative stress in applied basic research and clinical practice. Humana Press, Totowa, pp 153–167. doi: 10.1007/978-1-60327-514-9_10
  186. Simantov R (1989) Glutamate neurotoxicity in culture depends on the presence of glutamine: implications for the role of glial cells in normal and pathological brain development. J Neurochem 52(6):1694–1699PubMedCrossRefGoogle Scholar
  187. Slee EA, Harte MT, Kluck RM, Wolf BB, Casiano CA, Newmeyer DD, Wang HG, Reed JC, Nicholson DW, Alnemri ES, Green DR, Martin SJ (1999) Ordering the cytochrome c-initiated caspase cascade: hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner. J Cell Biol 144(2):281–292PubMedCrossRefGoogle Scholar
  188. Slivka A, Mytilineou C, Cohen G (1987) Histochemical evaluation of glutathione in brain. Brain Res 409(2):275–284PubMedCrossRefGoogle Scholar
  189. Stadtman ER (1992) Protein oxidation and aging. Science 257(5074):1220–1224PubMedCrossRefGoogle Scholar
  190. Stocker R, Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84(4):1381–1478. doi: 10.1152/physrev.00047.2003 PubMedCrossRefGoogle Scholar
  191. Sun SC, Ganchi PA, Beraud C, Ballard DW, Greene WC (1994) Autoregulation of the NF-kappa B transactivator RelA (p65) by multiple cytoplasmic inhibitors containing ankyrin motifs. Proc Natl Acad Sci USA 91(4):1346–1350PubMedCrossRefGoogle Scholar
  192. Susin SA, Zamzami N, Kroemer G (1998) Mitochondria as regulators of apoptosis: doubt no more. Biochim Biophys Acta 1366(1–2):151–165PubMedGoogle Scholar
  193. Suzuki YJ, Forman HJ, Sevanian A (1997) Oxidants as stimulators of signal transduction. Free Radic Biol Med 22(1–2):269–285PubMedCrossRefGoogle Scholar
  194. Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32(8):1870–1874PubMedGoogle Scholar
  195. Thanos D, Maniatis T (1995) NF-kappa B: a lesson in family values. Cell 80(4):529–532PubMedCrossRefGoogle Scholar
  196. Toyokuni S (1999) Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int 49(2):91–102PubMedCrossRefGoogle Scholar
  197. Trushina E, McMurray CT (2007) Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Neuroscience 145(4):1233–1248. doi: 10.1016/j.neuroscience.2006.10.056 PubMedCrossRefGoogle Scholar
  198. Van der Vliet A, Bast A (1992) Effect of oxidative stress on receptors and signal transmission. Chem Biol Interact 85(2–3):95–116PubMedCrossRefGoogle Scholar
  199. Velliquette RA, O’Connor T, Vassar R (2005) Energy inhibition elevates beta-secretase levels and activity and is potentially amyloidogenic in APP transgenic mice: possible early events in Alzheimer’s disease pathogenesis. J Neurosci 25(47):10874–10883. doi: 10.1523/JNEUROSCI.2350-05.2005 PubMedCrossRefGoogle Scholar
  200. Vignini A (2011) Stroke and oxidative stress. In: Gadoth N, Göbel HH (eds) Oxidative stress and free radical damage in neurology. Oxidative stress in applied basic research and clinical practice. Humana Press, Totowa, pp 137–152. doi: 10.1007/978-1-60327-514-9_9
  201. Wertz IE, Hanley MR (1996) Diverse molecular provocation of programmed cell death. Trends Biochem Sci 21(10):359–364PubMedGoogle Scholar
  202. White AR, Multhaup G, Galatis D, McKinstry WJ, Parker MW, Pipkorn R, Beyreuther K, Masters CL, Cappai R (2002) Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer’s disease amyloid precursor protein. J Neurosci 22(2):365–376PubMedGoogle Scholar
  203. White BC, Sullivan JM, DeGracia DJ, O’Neil BJ, Neumar RW, Grossman LI, Rafols JA, Krause GS (2000) Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci 179(S1–2):1–33PubMedCrossRefGoogle Scholar
  204. Williams CS, DuBois RN (1996) Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 270(3 Pt 1):G393–G400PubMedGoogle Scholar
  205. Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306PubMedCrossRefGoogle Scholar
  206. Yang JC, Cortopassi GA (1998) Induction of the mitochondrial permeability transition causes release of the apoptogenic factor cytochrome c. Free Radic Biol Med 24(4):624–631PubMedCrossRefGoogle Scholar
  207. Yeon JA, Kim SJ (2010) Neuroprotective effect of taurine against oxidative stress-induced damages in neuronal cells. Biomol Ther 18(1):24–31. doi: 10.4062/biomolther.2010.18.1.024 CrossRefGoogle Scholar
  208. Yoshida H, Kong YY, Yoshida R, Elia AJ, Hakem A, Hakem R, Penninger JM, Mak TW (1998) Apaf1 is required for mitochondrial pathways of apoptosis and brain development. Cell 94(6):739–750PubMedCrossRefGoogle Scholar
  209. Zamzami N, Susin SA, Marchetti P, Hirsch T, Gomez-Monterrey I, Castedo M, Kroemer G (1996) Mitochondrial control of nuclear apoptosis. J Exp Med 183(4):1533–1544PubMedCrossRefGoogle Scholar
  210. Zarkovic K (2003) 4-hydroxynonenal and neurodegenerative diseases. Mol Aspects Med 24(4–5):293–303PubMedCrossRefGoogle Scholar
  211. Zhu D, Tan KS, Zhang X, Sun AY, Sun GY, Lee JC (2005) Hydrogen peroxide alters membrane and cytoskeleton properties and increases intercellular connections in astrocytes. J Cell Sci 118(Pt 16):3695–3703PubMedCrossRefGoogle Scholar
  212. Zhu X, Raina AK, Lee HG, Casadesus G, Smith MA, Perry G (2004) Oxidative stress signalling in Alzheimer’s disease. Brain Res 1000(1–2):32–39. doi: 10.1016/j.brainres.2004.01.012 PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of Pharmacology and Toxicology, Metabolic Diseases Research Laboratory, School of DentistryKyung Hee UniversitySeoulRepublic of Korea

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