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

Abstract

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.

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References

  • 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]

    PubMed  CAS  Article  Google Scholar 

  • 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):295–307

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Andreyev AY, Kushnareva YE, Starkov AA (2005) Mitochondrial metabolism of reactive oxygen species. Biochemistry (Mosc) 70(2):200–214

    CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Baeuerle PA, Baltimore D (1996) NF-kappa B: ten years after. Cell 87(1):13–20

    PubMed  CAS  Article  Google Scholar 

  • 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):1867–1873

    PubMed  CAS  Article  Google Scholar 

  • Banati RB, Gehrmann J, Schubert P, Kreutzberg GW (1993) Cytotoxicity of microglia. Glia 7(1):111–118. doi:10.1002/glia.440070117

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Beal MF (1996) Mitochondria, free radicals, and neurodegeneration. Curr Opin Neurobiol 6(5):661–666

    PubMed  CAS  Article  Google Scholar 

  • Beal MF (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci 23(7):298–304

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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/j.ceb.2009.04.002

    PubMed  CAS  Article  Google Scholar 

  • Beckman JS (1996) Oxidative damage and tyrosine nitration from peroxynitrite. Chem Res Toxicol 9(5):836–844. doi:10.1021/tx9501445

    PubMed  CAS  Article  Google Scholar 

  • 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):944–950

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):281–296

    PubMed  CAS  Article  Google Scholar 

  • Bergeron C (1995) Oxidative stress: its role in the pathogenesis of amyotrophic lateral sclerosis. J Neurol Sci 129(Suppl):81–84

    PubMed  Article  Google Scholar 

  • Bjelland S, Seeberg E (2003) Mutagenicity, toxicity and repair of DNA base damage induced by oxidation. Mutat Res 531(1–2):37–80

    PubMed  CAS  Google Scholar 

  • 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):995–1001

    PubMed  CAS  Article  Google Scholar 

  • 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):99–105

    PubMed  CAS  Google Scholar 

  • 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):2322–2325

    PubMed  CAS  Article  Google Scholar 

  • Brigelius-Flohe R (1999) Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 27(9–10):951–965

    PubMed  CAS  Article  Google Scholar 

  • Browne SE, Ferrante RJ, Beal MF (1999) Oxidative stress in Huntington’s disease. Brain Pathol 9(1):147–163

    PubMed  CAS  Article  Google Scholar 

  • 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):857–868

    PubMed  CAS  Article  Google Scholar 

  • Brunk UT, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33(5):611–619

    PubMed  CAS  Article  Google Scholar 

  • Burke RE (1999) Parkinson’s disease. In: Koliatsos VE, Ratan RR (eds) Cell death and diseases of the nervous system. Humana Press, Totowa, pp 459–475

    Chapter  Google Scholar 

  • Butterfield DA, Kanski J (2001) Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev 122(9):945–962

    PubMed  CAS  Article  Google Scholar 

  • Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15(1):7–10

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Chan PH (2004) Mitochondria and neuronal death/survival signaling pathways in cerebral ischemia. Neurochem Res 29(11):1943–1949

    PubMed  CAS  Article  Google Scholar 

  • 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

  • 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):4914–4928

    PubMed  CAS  Google Scholar 

  • 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

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Coyle JT, Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262(5134):689–695

    PubMed  CAS  Article  Google Scholar 

  • 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):955–967

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Dawson VL, Dawson TM (1996) Nitric oxide neurotoxicity. J Chem Neuroanat 10(3–4):179–190

    PubMed  CAS  Article  Google Scholar 

  • 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):841–847

    PubMed  Article  Google Scholar 

  • 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):43–51

    PubMed  CAS  Article  Google Scholar 

  • Desagher S, Glowinski J, Premont J (1996) Astrocytes protect neurons from hydrogen peroxide toxicity. J Neurosci 16(8):2553–2562

    PubMed  CAS  Google Scholar 

  • 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):7–15

    PubMed  CAS  Article  Google Scholar 

  • 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):4912–4916

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):1063–1073

    PubMed  CAS  Google Scholar 

  • Ebadi M, Srinivasan SK, Baxi MD (1996) Oxidative stress and antioxidant therapy in Parkinson’s disease. Prog Neurobiol 48(1):1–19

    PubMed  CAS  Article  Google Scholar 

  • Eguchi Y, Shimizu S, Tsujimoto Y (1997) Intracellular ATP levels determine cell death fate by apoptosis or necrosis. Cancer Res 57(10):1835–1840

    PubMed  CAS  Google Scholar 

  • Emerit J, Edeas M, Bricaire F (2004) Neurodegenerative diseases and oxidative stress. Biomed Pharmacother 58(1):39–46

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):169–177

    PubMed  CAS  Article  Google Scholar 

  • 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):2064–2074

    PubMed  CAS  Article  Google Scholar 

  • Fields RD, Stevens-Graham B (2002) New insights into neuron-glia communication. Science 298(5593):556–562. doi:10.1126/science.298.5593.556

    PubMed  CAS  Article  Google Scholar 

  • Finkelstein E, Rosen GM, Rauckman EJ (1980) Spin trapping of superoxide and hydroxyl radical: practical aspects. Arch Biochem Biophys 200(1):1–16

    PubMed  CAS  Article  Google Scholar 

  • 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

  • Floyd RA (1999) Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med 222(3):236–245

    PubMed  CAS  Article  Google Scholar 

  • 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–S27

    PubMed  CAS  Article  Google Scholar 

  • 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):155–158

    PubMed  CAS  Article  Google Scholar 

  • Fridovich I (1986) Superoxide dismutases. Adv Enzymol Relat Areas Mol Biol 58:61–97

    PubMed  CAS  Google Scholar 

  • 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

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Gabbita SP, Lovell MA, Markesbery WR (1998) Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J Neurochem 71(5):2034–2040

    PubMed  CAS  Article  Google Scholar 

  • 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):128–136

    PubMed  CAS  Article  Google Scholar 

  • Goldberg AL (2003) Protein degradation and protection against misfolded or damaged proteins. Nature 426(6968):895–899. doi:10.1038/nature02263

    PubMed  CAS  Article  Google Scholar 

  • Gorman AM, McGowan A, O’Neill C, Cotter T (1996) Oxidative stress and apoptosis in neurodegeneration. J Neurol Sci 139(Suppl):45–52

    PubMed  Article  Google Scholar 

  • Gotz ME, Kunig G, Riederer P, Youdim MB (1994) Oxidative stress: free radical production in neural degeneration. Pharmacol Ther 63(1):37–122

    PubMed  CAS  Article  Google Scholar 

  • Greenamyre JT (1986) The role of glutamate in neurotransmission and in neurologic disease. Arch Neurol 43(10):1058–1063

    PubMed  CAS  Article  Google Scholar 

  • Grunewald T, Beal MF (1999) Bioenergetics in Huntington’s disease. Ann N Y Acad Sci 893:203–213

    PubMed  CAS  Article  Google Scholar 

  • 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):283–296

    PubMed  CAS  Google Scholar 

  • Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59(5):1609–1623

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Halliwell B, Clement MV, Long LH (2000) Hydrogen peroxide in the human body. FEBS Lett 486(1):10–13

    PubMed  CAS  Article  Google Scholar 

  • Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. Trends Neurosci 8:22–26. doi:10.1016/0166-2236(85)90010-4

    CAS  Article  Google Scholar 

  • Halliwell B, Gutteridge JMC (1999) Free radicals in biology and medicine, 3rd edn. Oxford science publications, Clarendon Press, Oxford University Press, Oxford

    Google Scholar 

  • 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):193–201

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069. doi:10.1146/annurev.bi.54.070185.005055

    PubMed  CAS  Article  Google Scholar 

  • Hazen SL, Hsu FF, Gaut JP, Crowley JR, Heinecke JW (1999) Modification of proteins and lipids by myeloperoxidase. Methods Enzymol 300:88–105

    PubMed  CAS  Article  Google Scholar 

  • 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 68:193–205

    CAS  Article  Google Scholar 

  • 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):243–245

    PubMed  CAS  Article  Google Scholar 

  • 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):8126–8132

    PubMed  CAS  Google Scholar 

  • 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):RC215

    PubMed  Google Scholar 

  • Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75(2):241–251

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):1338–1348

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Imlay JA (2003) Pathways of oxidative damage. Annu Rev Microbiol 57:395–418. doi:10.1146/annurev.micro.57.030502.090938

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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):321–327

    PubMed  CAS  Article  Google Scholar 

  • 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

  • Jaeschke H (1995) Mechanisms of oxidant stress-induced acute tissue injury. Proc Soc Exp Biol Med 209(2):104–111

    PubMed  CAS  Google Scholar 

  • Jenner P, Olanow CW (1996) Oxidative stress and the pathogenesis of Parkinson’s disease. Neurology 47(6 Suppl 3):S161–S170

    PubMed  CAS  Article  Google Scholar 

  • Jenner P, Olanow CW (1998) Understanding cell death in Parkinson’s disease. Ann Neurol 44(3 Suppl 1):S72–S84

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Kannan K, Jain SK (2000) Oxidative stress and apoptosis. Pathophysiology 7(3):153–163

    PubMed  CAS  Article  Google Scholar 

  • Kehrer JP, Lund LG (1994) Cellular reducing equivalents and oxidative stress. Free Radic Biol Med 17(1):65–75

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Kerr JF, Wyllie AH, Currie AR (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26(4):239–257

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  Article  Google Scholar 

  • Klein JA, Ackerman SL (2003) Oxidative stress, cell cycle, and neurodegeneration. J Clin Invest 111(6):785–793. doi:10.1172/JCI18182

    PubMed  CAS  Google Scholar 

  • 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):1132–1136

    PubMed  CAS  Article  Google Scholar 

  • Kohen R, Gati I (2000) Skin low molecular weight antioxidants and their role in aging and in oxidative stress. Toxicology 148(2–3):149–157

    PubMed  CAS  Article  Google Scholar 

  • Kohen R, Nyska A (2002) Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. Toxicol Pathol 30(6):620–650

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Koutsilieri E, Scheller C, Tribl F, Riederer P (2002) Degeneration of neuronal cells due to oxidative stress–microglial contribution. Parkinsonism Relat Disord 8(6):401–406

    PubMed  CAS  Article  Google Scholar 

  • 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):549–561

    PubMed  CAS  Article  Google Scholar 

  • Langston JW, Ballard P, Tetrud JW, Irwin I (1983) Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 219(4587):979–980

    PubMed  CAS  Article  Google Scholar 

  • Lehtinen MK, Bonni A (2006) Modeling oxidative stress in the central nervous system. Curr Mol Med 6(8):871–881

    PubMed  CAS  Article  Google Scholar 

  • 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):1481–1486

    PubMed  CAS  Article  Google Scholar 

  • 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):203–214

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Lewen A, Matz P, Chan PH (2000) Free radical pathways in CNS injury. J Neurotrauma 17(10):871–890

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):479–489

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443(7113):787–795. doi:10.1038/nature05292

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):37–44

    PubMed  CAS  Article  Google Scholar 

  • Love S, Barber R, Wilcock GK (1998) Apoptosis and expression of DNA repair proteins in ischaemic brain injury in man. Neuroreport 9(6):955–959

    PubMed  CAS  Article  Google Scholar 

  • 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):771–776

    PubMed  CAS  Article  Google Scholar 

  • Macmillan-Crow LA, Cruthirds DL (2001) Invited review: manganese superoxide dismutase in disease. Free Radic Res 34(4):325–336

    PubMed  CAS  Article  Google Scholar 

  • 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

    CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Mattson MP (2004) Metal-catalyzed disruption of membrane protein and lipid signaling in the pathogenesis of neurodegenerative disorders. Ann N Y Acad Sci 1012:37–50

    PubMed  CAS  Article  Google Scholar 

  • Mattson MP, Duan W, Pedersen WA, Culmsee C (2001) Neurodegenerative disorders and ischemic brain diseases. Apoptosis 6(1–2):69–81

    PubMed  CAS  Article  Google Scholar 

  • 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 893:154–175

    PubMed  CAS  Article  Google Scholar 

  • McConkey DJ (1998) Biochemical determinants of apoptosis and necrosis. Toxicol Lett 99(3):157–168

    PubMed  CAS  Article  Google Scholar 

  • Meister A (1992) On the antioxidant effects of ascorbic acid and glutathione. Biochem Pharmacol 44(10):1905–1915

    PubMed  CAS  Article  Google Scholar 

  • Meister A (1995) Glutathione metabolism. Methods Enzymol 251:3–7

    PubMed  CAS  Article  Google Scholar 

  • Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760. doi:10.1146/annurev.bi.52.070183.003431

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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]

    PubMed  CAS  Article  Google Scholar 

  • 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):1450–1455

    PubMed  CAS  Article  Google Scholar 

  • Moncada S, Higgs A (1993) The l-arginine-nitric oxide pathway. N Engl J Med 329(27):2002–2012. doi:10.1056/NEJM199312303292706

    PubMed  CAS  Article  Google Scholar 

  • 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):1709–1715

    PubMed  CAS  Article  Google Scholar 

  • Morel Y, Barouki R (1999) Repression of gene expression by oxidative stress. Biochem J 342(Pt 3):481–496

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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 23–59

    Google Scholar 

  • 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):205–213

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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

  • 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):3659–3668

    PubMed  CAS  Google Scholar 

  • Naoi M, Dostert P, Yoshida M, Nagatsu T (1993) N-methylated tetrahydroisoquinolines as dopaminergic neurotoxins. Adv Neurol 60:212–217

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):4177–4182

    PubMed  CAS  Google Scholar 

  • 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):759–767

    PubMed  CAS  Google Scholar 

  • O’Neill GP, Ford-Hutchinson AW (1993) Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 330(2):156–160

    PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95(2):351–358

    PubMed  CAS  Article  Google Scholar 

  • Olanow CW (1992) An introduction to the free radical hypothesis in Parkinson’s disease. Ann Neurol 32(Suppl):S2–S9

    PubMed  CAS  Article  Google Scholar 

  • Olanow CW (1993) A radical hypothesis for neurodegeneration. Trends Neurosci 16(11):439–444

    PubMed  CAS  Article  Google Scholar 

  • Olney JW (1989) Excitatory amino acids and neuropsychiatric disorders. Biol Psychiatry 26(5):505–525

    PubMed  CAS  Article  Google Scholar 

  • 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 1012:51–64

    PubMed  CAS  Article  Google Scholar 

  • 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 854:277–290

    PubMed  CAS  Article  Google Scholar 

  • Orrenius S, McConkey DJ, Bellomo G, Nicotera P (1989) Role of Ca2+ in toxic cell killing. Trends Pharmacol Sci 10(7):281–285

    PubMed  CAS  Article  Google Scholar 

  • Palmieri B, Sblendorio V (2007) Oxidative stress tests: overview on reliability and use. Part I. Eur Rev Med Pharmacol Sci 11(5):309–342

    PubMed  CAS  Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • 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):131–135

    PubMed  CAS  Google Scholar 

  • Perry TL, Hansen S (1990) What excitotoxin kills striatal neurons in Huntington’s disease? Clues from neurochemical studies. Neurology 40(1):20–24

    PubMed  CAS  Article  Google Scholar 

  • 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

    CAS  Article  Google Scholar 

  • 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):695–702

    PubMed  CAS  Article  Google Scholar 

  • 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):53–56

    PubMed  CAS  Article  Google Scholar 

  • 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):478–493

    PubMed  Article  Google Scholar 

  • 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):7420–7426

    PubMed  CAS  Article  Google Scholar 

  • Rao AV, Balachandran B (2002) Role of oxidative stress and antioxidants in neurodegenerative diseases. Nutr Neurosci 5(5):291–309

    PubMed  CAS  Article  Google Scholar 

  • Reed DJ, Savage MK (1995) Influence of metabolic inhibitors on mitochondrial permeability transition and glutathione status. Biochim Biophys Acta 1271(1):43–50

    PubMed  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Richter C (1993) Pro-oxidants and mitochondrial Ca2+: their relationship to apoptosis and oncogenesis. FEBS Lett 325(1–2):104–107

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):1375–1389

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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):1171–1178

    PubMed  CAS  Google Scholar 

  • 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):270–279

    PubMed  CAS  Article  Google Scholar 

  • 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 309:133–152

    PubMed  CAS  Article  Google Scholar 

  • Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21(1):172–188. doi:10.1021/tx700210j

    PubMed  Article  Google Scholar 

  • Scandalios JG (2002) Oxidative stress responses—what have genome-scale studies taught us? Genome Biol 3(7):REVIEWS1019

    Google Scholar 

  • 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–S98

    PubMed  CAS  Google Scholar 

  • 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):4079–4081

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Sies H (1985) Oxidative stress: introductory remarks. In: Sies H (ed) Oxidative stress. Academic Press, Orlando, pp 1–8

  • Sies H (1986) Biochemistry of oxidative stress. Angew Chem 25(12):1058–1071. doi:10.1002/anie.198610581

    Article  Google Scholar 

  • 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

  • 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):1694–1699

    PubMed  CAS  Article  Google Scholar 

  • 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):281–292

    PubMed  CAS  Article  Google Scholar 

  • Slivka A, Mytilineou C, Cohen G (1987) Histochemical evaluation of glutathione in brain. Brain Res 409(2):275–284

    PubMed  CAS  Article  Google Scholar 

  • Stadtman ER (1992) Protein oxidation and aging. Science 257(5074):1220–1224

    PubMed  CAS  Article  Google Scholar 

  • Stocker R, Keaney JF Jr (2004) Role of oxidative modifications in atherosclerosis. Physiol Rev 84(4):1381–1478. doi:10.1152/physrev.00047.2003

    PubMed  CAS  Article  Google Scholar 

  • 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):1346–1350

    PubMed  CAS  Article  Google Scholar 

  • Susin SA, Zamzami N, Kroemer G (1998) Mitochondria as regulators of apoptosis: doubt no more. Biochim Biophys Acta 1366(1–2):151–165

    PubMed  CAS  Google Scholar 

  • Suzuki YJ, Forman HJ, Sevanian A (1997) Oxidants as stimulators of signal transduction. Free Radic Biol Med 22(1–2):269–285

    PubMed  CAS  Article  Google Scholar 

  • Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32(8):1870–1874

    PubMed  CAS  Google Scholar 

  • Thanos D, Maniatis T (1995) NF-kappa B: a lesson in family values. Cell 80(4):529–532

    PubMed  CAS  Article  Google Scholar 

  • Toyokuni S (1999) Reactive oxygen species-induced molecular damage and its application in pathology. Pathol Int 49(2):91–102

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • Van der Vliet A, Bast A (1992) Effect of oxidative stress on receptors and signal transmission. Chem Biol Interact 85(2–3):95–116

    PubMed  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

  • 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

  • Wertz IE, Hanley MR (1996) Diverse molecular provocation of programmed cell death. Trends Biochem Sci 21(10):359–364

    PubMed  CAS  Google Scholar 

  • 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):365–376

    PubMed  CAS  Google Scholar 

  • 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):1–33

    PubMed  CAS  Article  Google Scholar 

  • Williams CS, DuBois RN (1996) Prostaglandin endoperoxide synthase: why two isoforms? Am J Physiol 270(3 Pt 1):G393–G400

    PubMed  CAS  Google Scholar 

  • Wyllie AH, Kerr JF, Currie AR (1980) Cell death: the significance of apoptosis. Int Rev Cytol 68:251–306

    PubMed  CAS  Article  Google Scholar 

  • 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):624–631

    PubMed  CAS  Article  Google Scholar 

  • 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

    CAS  Article  Google Scholar 

  • 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):739–750

    PubMed  CAS  Article  Google Scholar 

  • 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):1533–1544

    PubMed  CAS  Article  Google Scholar 

  • Zarkovic K (2003) 4-hydroxynonenal and neurodegenerative diseases. Mol Aspects Med 24(4–5):293–303

    PubMed  CAS  Article  Google Scholar 

  • 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):3695–3703

    PubMed  CAS  Article  Google Scholar 

  • 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

    PubMed  CAS  Article  Google Scholar 

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Acknowledgments

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

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Ramalingam, M., Kim, SJ. Reactive oxygen/nitrogen species and their functional correlations in neurodegenerative diseases. J Neural Transm 119, 891–910 (2012). https://doi.org/10.1007/s00702-011-0758-7

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Keywords

  • Free radicals
  • Neurons
  • Apoptosis
  • Necrosis
  • Signaling
  • Neurodegeneration