Top

Published in:

01-10-2012 | Review Article

Oxidative Damage to RNA in Aging and Neurodegenerative Disorders

Authors: Akihiko Nunomura, Paula I. Moreira, Rudy J. Castellani, Hyoung-gon Lee, Xiongwei Zhu, Mark A. Smith, George Perry

Published in: Neurotoxicity Research | Issue 3/2012

Abstract

An age-associated increase in oxidative damage to nucleic acids, predominantly to RNA, has been recently demonstrated in neurons of human and rodent brains, which may play a fundamental role in the development of age-associated neurodegeneration. Indeed, more prominent levels of neuronal RNA oxidation compared to normal aging have been described in neurodegenerative disorders including Alzheimer disease, Parkinson disease, dementia with Lewy bodies, and amyotrophic lateral sclerosis. Moreover, oxidative damage to RNA has been found also in cellular and animal model of neurodegeneration. Oxidative RNA modification can occur not only in protein-coding RNAs but also in non-coding RNAs that are recently revealed to contribute towards the complexity of the mammalian brain. It has been hypothesized that RNA oxidation causes aberrant expression of microRNAs and proteins and subsequently initiates inappropriate cell fate pathways. While less lethal than mutations in the genome and not inheritable, such sublethal damage to cells might be associated with underlying mechanisms of degeneration, especially age-associated neurodegeneration. Of particular interest, the accumulating evidence obtained from studies on either human samples or experimental models coincidentally suggests that RNA oxidation is a feature in neurons of aging brain and more prominently observed in vulnerable neurons at early-stage of age-associated neurodegenerative disorders, indicating that RNA oxidation actively contributes to the background, the onset, and the development of the disorders. Further investigations aimed at understanding of the processing mechanisms related to oxidative RNA damage and its consequences may provide significant insights into the pathogenesis of neurodegenerative disorders and lead to better therapeutic strategies.

Aas PA, Otterlei M, Falnes PO et al (2003) Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 421:859–863PubMedCrossRef

Abe T, Tohgi H, Isobe C, Murata T, Sato C (2002) Remarkable increase in the concentration of 8-hydroxyguanosine in cerebrospinal fluid from patients with Alzheimer’s disease. J Neurosci Res 70:447–450PubMedCrossRef

Abe T, Isobe C, Murata T, Sato C, Tohgi H (2003) Alteration of 8-hydroxyguanosine concentrations in the cerebrospinal fluid and serum from patients with Parkinson’s disease. Neurosci Lett 336:105–108PubMedCrossRef

Aluise CD, Robinson RA, Beckett TL et al (2010) Preclinical Alzheimer disease; brain oxidative stress, Aβ peptide and proteomics. Neurobiol Dis 39:221–228PubMedCrossRef

Aluise CD, Robinson RA, Cai J, Pierce WM, Markesbery WR, Butterfield DA (2011) Redox proteomics analysis of brains from subjects with amnestic mild cognitive impairment compared to brains from subjects with preclinical Alzheimer’s disease; insights into memory loss in MCI. J Alzheimers Dis 23:257–269PubMed

Ames BN, Gold LS (1991) Endogenous mutagens and the causes of aging and cancer. Mutat Res 250:3–16PubMedCrossRef

Andersen JK (2004) Oxidative stress in neurodegeneration: cause or consequence? Nat Med 10(Suppl):S18–S25PubMedCrossRef

Andreoli R, Mutti A, Goldoni M, Manini P, Apostoli P, De Palma G (2011) Reference ranges of urinary biomarkers of oxidized guanine in (2′-deoxy)ribonucleotides and nucleic acids. Free Radic Biol Med 50:254–261PubMedCrossRef

Barber SC, Mead RJ, Shaw PJ (2006) Oxidative stress in ALS: a mechanism of neurodegeneration and a therapeutic target. Biochim Biophys Acta 1762:1051–1067PubMedCrossRef

Barciszewski J, Barciszewska MZ, Siboska G, Rattan SI, Clark BF (1999) Some unusual nucleic acid bases are products of hydroxyl radical oxidation of DNA and RNA. Mol Biol Rep 26:231–238PubMedCrossRef

Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214PubMedCrossRef

Bellacosa A, Moss EG (2003) RNA repair: damage control. Curr Biol 13:R482–R484PubMedCrossRef

Berg D, Roggendorf W, Schroder U et al (2002) Echogenicity of the substantia nigra: association with increased iron content and marker for susceptibility to nigrostriatal injury. Arch Neurol 59:999–1005PubMedCrossRef

Bradley MA, Markesbery WR, Lovell MA (2010) Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease. Free Radic Biol Med 48:1570–1576PubMedCrossRef

Brégeon D, Sarasin A (2005) Hypothetical role of RNA damage avoidance in preventing human disease. Mutat Res 577:293–302PubMedCrossRef

Broedbaek K, Poulsen HE, Weimann A et al (2009) Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis. Free Radic Biol Med 47:1230–1233PubMedCrossRef

Broedbaek K, Siersma V, Henriksen T et al (2011) Urinary markers of nucleic acid oxidation and long-term mortality of newly diagnosed type 2 diabetic patients. Diabetes Care 34:2594–2596PubMedCrossRef

Butterfield DA, Reed TT, Perluigi M et al (2007) Elevated levels of 3-nitrotyrosine in brain from subjects with amnestic mild cognitive impairment: implications for the role of nitration in the progression of Alzheimer’s disease. Brain Res 1148:243–248PubMedCrossRef

Calabrese V, Cornelius C, Dinkova-Kostova AT, Calabrese EJ, Mattson MP (2010) Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal 13:1763–1811PubMedCrossRef

Calabrese V, Cornelius C, Dinkova-Kostova AT et al (2012) Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta 1822:753–783PubMedCrossRef

Cao X, Yeo G, Muotri AR, Kuwabara T, Gage FH (2006) Noncoding RNAs in the mammalian central nervous system. Annu Rev Neurosci 29:77–103PubMedCrossRef

Casadesus G, Smith MA, Basu S et al (2007) Increased isoprostane and prostaglandin are prominent in neurons in Alzheimer disease. Mol Neurodegener 2:2PubMedCrossRef

Castellani RJ, Harris PL, Sayre LM et al (2001) Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine. Free Radic Biol Med 31:175–180PubMedCrossRef

Chang Y, Kong Q, Shan X et al (2008) Messenger RNA oxidation occurs early in disease pathogenesis and promotes motor neuron degeneration in ALS. PLoS ONE 3:e2849PubMedCrossRef

Che Y, Wang JF, Shao L, Young T (2010) Oxidative damage to RNA but not DNA in the hippocampus of patients with major mental illness. J Psychiatry Neurosci 35:296–302PubMedCrossRef

Cooke MS, Olinski R, Evans MD (2006) Does measurement of oxidative damage to DNA have clinical significance? Clin Chim Acta 365:30–49PubMedCrossRef

Costa FF (2005) Non-coding RNAs: new players in eukaryotic biology. Gene 357:83–94PubMedCrossRef

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

Cui L, Hofer T, Rani A, Leeuwenburgh C, Foster TC (2009) Comparison of lifelong and late life exercise on oxidative stress in the cerebellum. Neurobiol Aging 30:903–909PubMedCrossRef

Deutscher MP (2006) Degradation of RNA in bacteria: comparison of mRNA and stable RNA. Nucleic Acids Res 34:659–666PubMedCrossRef

Ding Q, Dimayuga E, Markesbery WR, Keller JN (2004) Proteasome inhibition increases DNA and RNA oxidation in astrocyte and neuron cultures. J Neurochem 91:1211–1218PubMedCrossRef

Ding Q, Markesbery WR, Chen Q, Li F, Keller JN (2005) Ribosome dysfunction is an early event in Alzheimer’s disease. J Neurosci 25:9171–9175PubMedCrossRef

Ding Q, Markesbery WR, Cecarini V, Keller JN (2006) Decreased RNA, and increased RNA oxidation, in ribosomes from early Alzheimer’s disease. Neurochem Res 31:705–710PubMedCrossRef

Ding Q, Cecarini V, Keller JN (2007) Interplay between protein synthesis and degradation in the CNS: physiological and pathological implications. Trends Neurosci 30:31–36PubMedCrossRef

Evans MD, Dizdaroglu M, Cooke MS (2004) Oxidative DNA damage and disease: induction, repair and significance. Mutat Res 567:1–61PubMedCrossRef

Fiala ES, Conaway CC, Mathis JE (1989) Oxidative DNA and RNA damage in the livers of Sprague-Dawley rats treated with the hepatocarcinogen 2-nitropropane. Cancer Res 49:5518–5522PubMed

Foksinski M, Rozalski R, Guz J et al (2004) Urinary excretion of DNA repair products correlates with metabolic rates as well as with maximum life spans of different mammalian species. Free Radic Biol Med 37:1449–1454PubMedCrossRef

Furuta A, Iida T, Nakabeppu Y, Iwaki T (2001) Expression of hMTH1 in the hippocampi of control and Alzheimer’s disease. NeuroReport 12:2895–2899PubMedCrossRef

Gemma C, Vila J, Bachstetter A, Bickford PC (2007) Oxidative stress and the aging brain: from theory to prevention, Chapter 15. In: Riddle DR (ed) Brain aging: models, methods, and mechanisms. CRC Press, Boca Raton, FL

Gong X, Tao R, Li Z (2006) Quantification of RNA damage by reverse transcription polymerase chain reactions. Anal Biochem 357:58–67PubMedCrossRef

Görg B, Qvartskhava N, Keitel V et al (2008) Ammonia induces RNA oxidation in cultured astrocytes and brain in vivo. Hepatology 48:567–579PubMedCrossRef

Görg B, Qvartskhava N, Bidmon HJ et al (2010) Oxidative stress markers in the brain of patients with cirrhosis and hepatic encephalopathy. Hepatology 52:256–265PubMedCrossRef

Gu G, Reyes PE, Golden GT et al (2002) Mitochondrial DNA deletions/rearrangements in Parkinson disease and related neurodegenerative disorders. J Neuropathol Exp Neurol 61:634–639PubMed

Guentchev M, Siedlak SL, Jarius C et al (2002) Oxidative damage to nucleic acids in human prion disease. Neurobiol Dis 9:275–281PubMedCrossRef

Guidi I, Galimberti D, Lonati S et al (2006) Oxidative imbalance in patients with mild cognitive impairment and Alzheimer’s disease. Neurobiol Aging 27:262–269PubMedCrossRef

Gurney ME, Pu H, Chiu AY et al (1994) Motor neuron degeneration in mice that express a human Cu, Zn superoxide dismutase mutation. Science 264:1772–1775PubMedCrossRef

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

Hayakawa H, Sekiguchi M (2006) Human polynucleotide phosphorylase protein in response to oxidative stress. Biochemistry (Mosc) 45:6749–6755CrossRef

Hayakawa H, Hofer A, Thelander L et al (1999) Metabolic fate of oxidized guanine ribonucleotides in mammalian cells. Biochemistry (Mosc) 38:3610–3614CrossRef

Hayakawa H, Kuwano M, Sekiguchi M (2001) Specific binding of 8-oxoguanine-containing RNA to polynucleotide phosphorylase protein. Biochemistry (Mosc) 40:9977–9982CrossRef

Hayakawa H, Uchiumi T, Fukuda T et al (2002) Binding capacity of human YB-1 protein for RNA containing 8-oxoguanine. Biochemistry (Mosc) 41:12739–12744CrossRef

Hayakawa H, Fujikane A, Ito R, Matsumoto M, Nakayama KI, Sekiguchi M (2010) Human proteins that specifically bind to 8-oxoguanine-containing RNA and their responses to oxidative stress. Biochem Biophys Res Commun 403:220–224PubMedCrossRef

Hayashi M, Arai N, Satoh J et al (2002) Neurodegenerative mechanisms in subacute sclerosing panencephalitis. J Child Neurol 17:725–730PubMedCrossRef

Hayashi M, Araki S, Kohyama J, Shioda K, Fukatsu R (2005) Oxidative nucleotide damage and superoxide dismutase expression in the brains of xeroderma pigmentosum group A and Cockayne syndrome. Brain Dev 27:34–38PubMedCrossRef

Herrup K (2010) Reimagining Alzheimer’s disease—an age-based hypothesis. J Neurosci 30:16755–16762PubMedCrossRef

Hirai K, Aliev G, Nunomura A et al (2001) Mitochondrial abnormalities in Alzheimer’s disease. J Neurosci 21:3017–3023PubMed

Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R (2007) How common are the “common” neurologic disorders? Neurology 68:326–337PubMedCrossRef

Hofer T, Badouard C, Bajak E, Ravanat JL, Mattsson A, Cotgreave IA (2005) Hydrogen peroxide causes greater oxidation in cellular RNA than in DNA. Biol Chem 386:333–337PubMedCrossRef

Hofer T, Seo AY, Prudencio M, Leeuwenburgh C (2006) A method to determine RNA and DNA oxidation simultaneously by HPLC-ECD: greater RNA than DNA oxidation in rat liver after doxorubicin administration. Biol Chem 387:103–111PubMedCrossRef

Hofer T, Fontana L, Anton SD et al (2008a) Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans. Rejuvenation Res 11:793–799PubMedCrossRef

Hofer T, Marzetti E, Xu J et al (2008b) Increased iron content and RNA oxidative damage in skeletal muscle with aging and disuse atrophy. Exp Gerontol 43:563–570PubMedCrossRef

Hoffman WH, Siedlak SL, Wang Y, Castellani RJ, Smith MA (2011) Oxidative damage is present in the fatal brain edema of diabetic ketoacidosis. Brain Res 1369:194–202PubMedCrossRef

Holcomb DR, Ropp PA, Theil EC, Thorp HH (2010) Nature of guanine oxidation in RNA via the flash-quench technique versus direct oxidation by a metal oxo complex. Inorg Chem 49:786–795PubMedCrossRef

Honda K, Smith MA, Zhu X et al (2005) Ribosomal RNA in Alzheimer disease is oxidized by bound redox-active iron. J Biol Chem 280:20978–20986PubMedCrossRef

Honig LS, Kukull W, Mayeux R (2005) Atherosclerosis and AD: analysis of data from the US National Alzheimer’s Coordinating Center. Neurology 64:494–500PubMedCrossRef

Huang WL, King VR, Curran OE et al (2007) A combination of intravenous and dietary docosahexaenoic acid significantly improves outcome after spinal cord injury. Brain 130:3004–3019PubMedCrossRef

Ischiropoulos H, Beckman JS (2003) Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest 111:163–169PubMed

Ishibashi T, Hayakawa H, Ito R, Miyazawa M, Yamagata Y, Sekiguchi M (2005) Mammalian enzymes for preventing transcriptional errors caused by oxidative damage. Nucleic Acids Res 33:3779–3784PubMedCrossRef

Ito R, Hayakawa H, Sekiguchi M, Ishibashi T (2005) Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools. Biochemistry (Mosc) 44:6670–6674CrossRef

Jacobs AC, Resendiz MJ, Greenberg MM (2010) Direct strand scission from a nucleobase radical in RNA. J Am Chem Soc 132:3668–3669PubMedCrossRef

Javitch JA, D’Amato RJ, Strittmatter SM, Snyder SH (1985) Parkinsonism-inducing neurotoxin, N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: uptake of the metabolite N-methyl-4-phenylpyridine by dopamine neurons explains selective toxicity. Proc Natl Acad Sci USA 82:2173–2177PubMedCrossRef

Jenner P (2003) Oxidative stress in Parkinson’s disease. Ann Neurol 53(Suppl 3):S26–S36PubMedCrossRef

Joenje H (1989) Genetic toxicology of oxygen. Mutat Res 219:193–208PubMedCrossRef

Kajitani K, Yamaguchi H, Dan Y, Furuichi M, Kang D, Nakabeppu Y (2006) MTH1, an oxidized purine nucleoside triphosphatase, suppresses the accumulation of oxidative damage of nucleic acids in the hippocampal microglia during kainate-induced excitotoxicity. J Neurosci 26:1688–1698PubMedCrossRef

Kasai H, Crain PF, Kuchino Y, Nishimura S, Ootsuyama A, Tanooka H (1986) Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair. Carcinogenesis 7:1849–1851PubMedCrossRef

Kedersha N, Stoecklin G, Ayodele M et al (2005) Stress granules and processing bodies are dynamically linked sites of mRNP remodeling. J Cell Biol 169:871–884PubMedCrossRef

Keller JN, Schmitt FA, Scheff SW et al (2005) Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 64:1152–1156PubMedCrossRef

Kikuchi A, Takeda A, Onodera H et al (2002) Systemic increase of oxidative nucleic acid damage in Parkinson’s disease and multiple system atrophy. Neurobiol Dis 9:244–248PubMedCrossRef

King VR, Huang WL, Dyall SC, Curran OE, Priestley JV, Michael-Titus AT (2006) Omega-3 fatty acids improve recovery, whereas omega-6 fatty acids worsen outcome, after spinal cord injury in the adult rat. J Neurosci 26:4672–4680PubMedCrossRef

Krokan HE, Kavli B, Slupphaug G (2004) Novel aspects of macromolecular repair and relationship to human disease. J Mol Med 82:280–297PubMedCrossRef

Lee JW, Beebe K, Nangle LA et al (2006) Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration. Nature 443:50–55PubMedCrossRef

Li Z, Wu J, Deleo CJ (2006) RNA damage and surveillance under oxidative stress. IUBMB Life 58:581–588PubMedCrossRef

Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795PubMedCrossRef

Liu J, Head E, Gharib AM et al (2002) Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci USA 99:2356–2361PubMedCrossRef

Liu Q, Xie F, Rolston R et al (2007) Prevention and treatment of Alzheimer disease and aging: antioxidants. Mini Rev Med Chem 7:171–180PubMedCrossRef

Logroscino G, Beghi E, Zoccolella S et al (2005) Incidence of amyotrophic lateral sclerosis in southern Italy: a population based study. J Neurol Neurosurg Psychiatry 76:1094–1098PubMedCrossRef

Lovell MA, Markesbery WR (2008) Oxidatively modified RNA in mild cognitive impairment. Neurobiol Dis 29:169–175PubMedCrossRef

Lovell MA, Xiong S, Lyubartseva G, Markesbery WR (2009) Organoselenium (Sel-Plex diet) decreases amyloid burden and RNA and DNA oxidative damage in APP/PS1 mice. Free Radic Biol Med 46:1527–1533PubMedCrossRef

Lovell MA, Soman S, Bradley MA (2011) Oxidatively modified nucleic acids in preclinical Alzheimer’s disease (PCAD) brain. Mech Ageing Dev 132:443–448PubMedCrossRef

Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer’s disease: clinical trials and drug development. Lancet Neurol 9:702–716PubMedCrossRef

Manini P, De Palma G, Andreoli R et al (2009) Biomarkers of nucleic acid oxidation, polymorphism in, and expression of, hOGG1 gene in styrene-exposed workers. Toxicol Lett 190:41–47PubMedCrossRef

Manini P, De Palma G, Andreoli R et al (2010) Occupational exposure to low levels of benzene: biomarkers of exposure and nucleic acid oxidation and their modulation by polymorphic xenobiotic metabolizing enzymes. Toxicol Lett 193:229–235PubMedCrossRef

Martinet W, de Meyer GR, Herman AG, Kockx MM (2004) Reactive oxygen species induce RNA damage in human atherosclerosis. Eur J Clin Invest 34:323–327PubMedCrossRef

Mattson MP, Chan SL, Duan W (2002) Modification of brain aging and neurodegenerative disorders by genes, diet, and behavior. Physiol Rev 82:637–672PubMed

Mehler MF, Mattick JS (2006) Non-coding RNAs in the nervous system. J Physiol 575:333–341PubMedCrossRef

Mehler MF, Mattick JS (2007) Noncoding RNAs and RNA editing in brain development, functional diversification, and neurological disease. Physiol Rev 87:799–823PubMedCrossRef

Migliore L, Fontana I, Trippi F et al (2005) Oxidative DNA damage in peripheral leukocytes of mild cognitive impairment and AD patients. Neurobiol Aging 26:567–573PubMedCrossRef

Miyata R, Hayashi M, Tanuma N, Shioda K, Fukatsu R, Mizutani S (2008) Oxidative stress in neurodegeneration in dentatorubral-pallidoluysian atrophy. J Neurol Sci 264:133–139PubMedCrossRef

Moreira PI, Honda K, Zhu X et al (2006a) Brain and brawn: parallels in oxidative strength. Neurology 66(Suppl 1):S97–S101PubMedCrossRef

Moreira PI, Zhu X, Nunomura A, Smith MA, Perry G (2006b) Therapeutic options in Alzheimer’s disease. Expert Rev Neurother 6:897–910PubMedCrossRef

Moreira PI, Nunomura A, Nakamura M et al (2008) Nucleic acid oxidation in Alzheimer disease. Free Radic Biol Med 44:1493–1505PubMedCrossRef

Mundt JM, Hah SS, Sumbad RA, Schramm V, Henderson PT (2008) Incorporation of extracellular 8-oxodG into DNA and RNA requires purine nucleoside phosphorylase in MCF-7 cells. Nucleic Acids Res 36:228–236PubMedCrossRef

Nakabeppu Y, Tsuchimoto D, Ichinoe A et al (2004) Biological significance of the defense mechanisms against oxidative damage in nucleic acids caused by reactive oxygen species: from mitochondria to nuclei. Ann N Y Acad Sci 1011:101–111PubMedCrossRef

Nakabeppu Y, Kajitani K, Sakamoto K, Yamaguchi H, Tsuchimoto D (2006) MTH1, an oxidized purine nucleoside triphosphatase, prevents the cytotoxicity and neurotoxicity of oxidized purine nucleotides. DNA Repair (Amst) 5:761–772CrossRef

Nelson PT, Wang WX, Rajeev BW (2008) MicroRNAs (miRNAs) in neurodegenerative diseases. Brain Pathol 18:130–138PubMedCrossRef

Nunomura A, Perry G, Pappolla MA et al (1999) RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer’s disease. J Neurosci 19:1959–1964PubMed

Nunomura A, Perry G, Pappolla MA et al (2000) Neuronal oxidative stress precedes amyloid-β deposition in Down syndrome. J Neuropathol Exp Neurol 59:1011–1017PubMed

Nunomura A, Perry G, Aliev G et al (2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropathol Exp Neurol 60:759–767PubMed

Nunomura A, Chiba S, Kosaka K et al (2002) Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies. NeuroReport 13:2035–2039PubMedCrossRef

Nunomura A, Chiba S, Lippa CF et al (2004) Neuronal RNA oxidation is a prominent feature of familial Alzheimer’s disease. Neurobiol Dis 17:108–113PubMedCrossRef

Nunomura A, Castellani RJ, Zhu X, Moreira PI, Perry G, Smith MA (2006) Involvement of oxidative stress in Alzheimer disease. J Neuropathol Exp Neurol 65:631–641PubMedCrossRef

Nunomura A, Moreira PI, Lee HG et al (2007) Neuronal death and survival under oxidative stress in Alzheimer and Parkinson diseases. CNS Neurol Disord: Drug Targets 6:411–423CrossRef

Nunomura A, Tamaoki T, Tanaka K et al (2010) Intraneuronal amyloid β accumulation and oxidative damage to nucleic acids in Alzheimer disease. Neurobiol Dis 37:731–737PubMedCrossRef

Nunomura A, Tamaoki T, Motohashi N et al (2012) The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons. J Neuropathol Exp Neurol 71:233–241PubMedCrossRef

Park EM, Shigenaga MK, Degan P et al (1992) Assay of excised oxidative DNA lesions: isolation of 8-oxoguanine and its nucleoside derivatives from biological fluids with a monoclonal antibody column. Proc Natl Acad Sci USA 89:3375–3379PubMedCrossRef

Perkins DO, Jeffries C, Sullivan P (2005) Expanding the ‘central dogma’: the regulatory role of nonprotein coding genes and implications for the genetic liability to schizophrenia. Mol Psychiatry 10:69–78PubMedCrossRef

Perry G, Nunomura A, Cash AD et al (2002a) Reactive oxygen: its sources and significance in Alzheimer disease. J Neural Transm Suppl 62:69–75PubMed

Perry G, Nunomura A, Hirai K et al (2002b) Is oxidative damage the fundamental pathogenic mechanism of Alzheimer’s and other neurodegenerative diseases? Free Radic Biol Med 33:1475–1479PubMedCrossRef

Petersen RB, Siedlak SL, Lee HG et al (2005) Redox metals and oxidative abnormalities in human prion diseases. Acta Neuropathol 110:232–238PubMedCrossRef

Praticò D, Clark CM, Liun F, Rokach J, Lee VY, Trojanowski JQ (2002) Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Arch Neurol 59:972–976PubMedCrossRef

Rahkonen T, Eloniemi-Sulkava U, Rissanen S, Vatanen A, Viramo P, Sulkava R (2003) Dementia with Lewy bodies according to the consensus criteria in a general population aged 75 years or older. J Neurol Neurosurg Psychiatry 74:720–724PubMedCrossRef

Rhee Y, Valentine MR, Termini J (1995) Oxidative base damage in RNA detected by reverse transcriptase. Nucleic Acids Res 23:3275–3282PubMedCrossRef

Rinaldi P, Polidori MC, Metastasio A et al (2003) Plasma antioxidants are similarly depleted in mild cognitive impairment and in Alzheimer’s disease. Neurobiol Aging 24:915–919PubMedCrossRef

Rosen DR, Siddique T, Patterson D et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62PubMedCrossRef

Row BW, Liu R, Xu W, Kheirandish L, Gozal D (2003) Intermittent hypoxia is associated with oxidative stress and spatial learning deficits in the rat. Am J Respir Crit Care Med 167:1548–1553PubMedCrossRef

Satterlee JS, Barbee S, Jin P et al (2007) Noncoding RNAs in the Brain. J Neurosci 27:11856–11859PubMedCrossRef

Sayre LM, Zelasko DA, Harris PL, Perry G, Salomon RG, Smith MA (1997) 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer’s disease. J Neurochem 68:2092–2097PubMedCrossRef

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 309:133–152PubMedCrossRef

Sayre LM, Smith MA, Perry G (2001) Chemistry and biochemistry of oxidative stress in neurodegenerative disease. Curr Med Chem 8:721–738PubMed

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

Schneider JE Jr, Phillips JR, Pye Q, Maidt ML, Price S, Floyd RA (1993) Methylene blue and rose bengal photoinactivation of RNA bacteriophages: comparative studies of 8-oxoguanine formation in isolated RNA. Arch Biochem Biophys 301:91–97PubMedCrossRef

Schubert J, Wilmer JW (1991) Does hydrogen peroxide exist “free” in biological systems? Free Radic Biol Med 11:545–555PubMedCrossRef

Seo AY, Hofer T, Sung B, Judge S, Chung HY, Leeuwenburgh C (2006) Hepatic oxidative stress during aging: effects of 8% long-term calorie restriction and lifelong exercise. Antioxid Redox Signal 8:529–538PubMedCrossRef

Seo AY, Xu J, Servais S et al (2008) Mitochondrial iron accumulation with age and functional consequences. Aging Cell 7:706–716PubMedCrossRef

Shan X, Lin CL (2006) Quantification of oxidized RNAs in Alzheimer’s disease. Neurobiol Aging 27:657–662PubMedCrossRef

Shan X, Tashiro H, Lin CL (2003) The identification and characterization of oxidized RNAs in Alzheimer’s disease. J Neurosci 23:4913–4921PubMed

Shan X, Chang Y, Lin CL (2007) Messenger RNA oxidation is an early event preceding cell death and causes reduced protein expression. FASEB J 21:2753–2764PubMedCrossRef

Shao C, Xiong S, Li GM et al (2008) Altered 8-oxoguanine glycosylase in mild cognitive impairment and late-stage Alzheimer’s disease brain. Free Radic Biol Med 45:813–819PubMedCrossRef

Shen Z, Wu W, Hazen SL (2000) Activated leukocytes oxidatively damage DNA, RNA, and the nucleotide pool through halide-dependent formation of hydroxyl radical. Biochemistry (Mosc) 39:5474–5482CrossRef

Sheth U, Parker R (2003) Decapping and decay of messenger RNA occur in cytoplasmic processing bodies. Science 300:805–808PubMedCrossRef

Shi Q, Gibson GE (2011) Up-regulation of the mitochondrial malate dehydrogenase by oxidative stress is mediated by miR-743a. J Neurochem 118:440–448PubMedCrossRef

Shi F, Gan W, Nie B et al (2012) Greater nucleic acids oxidation in the temporal lobe than the frontal lobe in SAMP8. NeuroReport 23:508–512PubMedCrossRef

Shimura-Miura H, Hattori N, Kang D, Miyako K, Nakabeppu Y, Mizuno Y (1999) Increased 8-oxo-dGTPase in the mitochondria of substantia nigral neurons in Parkinson’s disease. Ann Neurol 46:920–924PubMedCrossRef

Smith MA, Perry G, Richey PL et al (1996) Oxidative damage in Alzheimer’s. Nature 382:120–121PubMedCrossRef

Smith MA, Nunomura A, Zhu X, Takeda A, Perry G (2000) Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease. Antioxid Redox Signal 2:413–420PubMedCrossRef

Sofic E, Riederer P, Heinsen H et al (1988) Increased iron (III) and total iron content in post mortem substantia nigra of parkinsonian brain. J Neural Transm 74:199–205PubMedCrossRef

Song XN, Zhang LQ, Liu DG et al (2011) Oxidative damage to RNA and expression patterns of MTH1 in the hippocampi of senescence-accelerated SAMP8 mice and Alzheimer’s disease patients. Neurochem Res 36:1558–1565PubMedCrossRef

Sperling RA, Aisen PS, Beckett LA et al (2011) Toward defining the preclinical stages of Alzheimer’s disease; recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292PubMedCrossRef

Szymanski M, Barciszewska MZ, Erdmann VA, Barciszewski J (2005) A new frontier for molecular medicine: noncoding RNAs. Biochim Biophys Acta 1756:65–75PubMed

Taddei F, Hayakawa H, Bouton M et al (1997) Counteraction by MutT protein of transcriptional errors caused by oxidative damage. Science 278:128–130PubMedCrossRef

Taft RJ, Pheasant M, Mattick JS (2007) The relationship between non-protein-coding DNA and eukaryotic complexity. BioEssays 29:288–299PubMedCrossRef

Takahashi MA, Asada K (1983) Superoxide anion permeability of phospholipid membranes and chloroplast thylakoids. Arch Biochem Biophys 226:558–566PubMedCrossRef

Tanaka M, Chock PB, Stadtman ER (2007) Oxidized messenger RNA induces translation errors. Proc Natl Acad Sci USA 104:66–71PubMedCrossRef

Tanaka M, Han S, Küpfer PA, Leumann CJ, Sonntag WE (2011a) Quantification of oxidized levels of specific RNA species using an aldehyde reactive probe. Anal Biochem 417:142–148PubMedCrossRef

Tanaka M, Han S, Küpfer PA, Leumann CJ, Sonntag WE (2011b) An assay for RNA oxidation induced abasic sites using the Aldehyde Reactive Probe. Free Radic Res 45:237–247PubMedCrossRef

Tateyama M, Takeda A, Onodera Y et al (2003) Oxidative stress and predominant Aβ42(43) deposition in myopathies with rimmed vacuoles. Acta Neuropathol 105:581–585PubMed

Taylor JP, Hardy J, Fischbeck KH (2002) Toxic proteins in neurodegenerative disease. Science 296:1991–1995PubMedCrossRef

van Leeuwen FW, de Kleijn DP, van den Hurk HH et al (1998) Frameshift mutants of β amyloid precursor protein and ubiquitin-B in Alzheimer’s and Down patients. Science 279:242–247PubMedCrossRef

Vascotto C, Fantini D, Romanello M et al (2009) APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. Mol Cell Biol 29:1834–1854PubMedCrossRef

Wamer WG, Wei RR (1997) In vitro photooxidation of nucleic acids by ultraviolet A radiation. Photochem Photobiol 65:560–563PubMedCrossRef

Wang Q, Yu S, Simonyi A, Sun GY, Sun AY (2005) Kainic acid-mediated excitotoxicity as a model for neurodegeneration. Mol Neurobiol 31:3–16PubMedCrossRef

Wang J, Markesbery WR, Lovell MA (2006) Increased oxidative damage in nuclear and mitochondrial DNA in mild cognitive impairment. J Neurochem 96:825–832PubMedCrossRef

Weidner AM, Bradley MA, Beckett TL et al (2011) RNA oxidation adducts 8-OHG and 8-OHA change with Aβ42 levels in late-stage Alzheimer’s disease. PLoS ONE 6(9):e24930PubMedCrossRef

Weimann A, Belling D, Poulsen HE (2002) Quantification of 8-oxo-guanine and guanine as the nucleobase, nucleoside and deoxynucleoside forms in human urine by high-performance liquid chromatography-electrospray tandem mass spectrometry. Nucleic Acids Res 30:e7PubMedCrossRef

Weissman L, Jo DG, Sørensen MM et al (2007) Defective DNA base excision repair in brain from individuals with Alzheimer’s disease and amnestic mild cognitive impairment. Nucleic Acids Res 35:5545–5555PubMedCrossRef

Wu J, Li Z (2008) Human polynucleotide phosphorylase reduces oxidative RNA damage and protects HeLa cell against oxidative stress. Biochem Biophys Res Commun 372:288–292PubMedCrossRef

Yamaguchi H, Kajitani K, Dan Y et al (2006) MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Cell Death Differ 13:551–563PubMedCrossRef

Yanagawa H, Ogawa Y, Ueno M (1992) Redox ribonucleosides. Isolation and characterization of 5-hydroxyuridine, 8-hydroxyguanosine, and 8-hydroxyadenosine from Torula yeast RNA. J Biol Chem 267:13320–13326PubMed

Yang WH, Bloch DB (2007) Probing the mRNA processing body using protein macroarrays and “autoantigenomics”. RNA 13:704–712PubMedCrossRef

Yin B, Whyatt RM, Perera FP, Randall MC, Cooper TB, Santella RM (1995) Determination of 8-hydroxydeoxyguanosine by an immunoaffinity chromatography-monoclonal antibody-based ELISA. Free Radic Biol Med 18:1023–1032PubMedCrossRef

Zhang J, Perry G, Smith MA et al (1999) Parkinson’s disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154:1423–1429PubMedCrossRef

Title: Oxidative Damage to RNA in Aging and Neurodegenerative Disorders
Authors: Akihiko Nunomura
Paula I. Moreira
Rudy J. Castellani
Hyoung-gon Lee
Xiongwei Zhu
Mark A. Smith
George Perry
Publication date: 01-10-2012
Publisher: Springer-Verlag
Published in: Neurotoxicity Research / Issue 3/2012
Print ISSN: 1029-8428
Electronic ISSN: 1476-3524
DOI: https://doi.org/10.1007/s12640-012-9331-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Oxidative Damage to RNA in Aging and Neurodegenerative Disorders

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 3/2012

Amyloid-β Production: Major Link Between Oxidative Stress and BACE1

Alzheimer’s Disease Pathologic Cascades: Who Comes First, What Drives What

Role of Cell Cycle Re-Entry in Neurons: A Common Apoptotic Mechanism of Neuronal Cell Death

Mark Smith: Pioneer of Alzheimer Disease Research

Cell Cycle Proteins in Brain in Mild Cognitive Impairment: Insights into Progression to Alzheimer Disease

Erratum to: Protective Effects of Nicotine Against Aminochrome-Induced Toxicity in Substantia Nigra Derived Cells: Implications for Parkinson’s Disease