Free radicals and brain aging

Clinics in Geriatric Medicine

Volumn 20, Issue 2, 2004, Pages 329-359

  Poon, H Fai ^a,b   Calabrese, Vittorio ^c   Scapagnini, Giovanni ^d   Butterfield, D Allan ^a,b  

^a UNIVERSITY OF KENTUCKY   (United States)

^b UNIVERSITY OF KENTUCKY   (United States)

^c UNIVERSITY OF CATANIA   (Italy)

^d INSTITUTE OF NEUROLOGICAL SCIENCES   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIOXIDANT; DNA; FREE RADICAL; GLUTATHIONE; HEAT SHOCK PROTEIN; HYDROGEN PEROXIDE; HYDROXYL RADICAL; HYPOCHLOROUS ACID; NITRIC OXIDE; NITROGEN DIOXIDE; PEROXYNITRITE; REACTIVE NITROGEN SPECIES; REACTIVE OXYGEN METABOLITE; SUPEROXIDE;

AGING; BRAIN; CELL DAMAGE; CORRELATION ANALYSIS; DEGENERATIVE DISEASE; HUMAN; LIPID PEROXIDATION; MITOCHONDRION; NONHUMAN; OXIDATION; PROTEIN BINDING; PROTEOMICS; REVIEW;

AGED; AGED, 80 AND OVER; AGING; ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; FEMALE; FREE RADICALS; GERIATRIC ASSESSMENT; HEAT-SHOCK PROTEINS; HUMANS; MALE; NITROGEN DIOXIDE; OXIDATIVE STRESS; PROGNOSIS; REACTIVE OXYGEN SPECIES; RESEARCH; SENSITIVITY AND SPECIFICITY;

EID: 2942559035     PISSN: 07490690     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cger.2004.02.005     Document Type: Review

References (263)

1. Ashok B.T., Ali R. The aging paradox: free radical theory of aging. Exp Gerontol. 34(3):1999;293-303
2. Sohal R.S., Mockett R.J., Orr W.C. Mechanisms of aging: an appraisal of the oxidative stress hypothesis. Free Radic Biol Med. 33(5):2002;575-586
3. Harman D. Aging: a theory based on free radical and radiation chemsitry. J Gerontol. 11:1956;298-300
4. Harman D. Prolongation of life: role of free radical reactions in aging. J Am Geriatr Soc. 17(8):1969;721-735
5. Gilgun-Sherki Y., Melamed E., Offen D. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology. 40(8):2001;959-975
6. Floyd R.A. Antioxidants, oxidative stress, and degenerative neurological disorders. Proc Soc Exp Biol Med. 222(3):1999;236-245
7. Calabrese V., Bates T.E., Stella A.M. NO synthase and NO-dependent signal pathways in brain aging and neurodegenerative disorders: the role of oxidant/antioxidant balance. Neurochem Res. 25(9-10):2000;1315-1341
8. Ventura B., et al. Control of oxidative phosphorylation by Complex I in rat liver mitochondria: implications for aging. Biochim Biophys Acta. 1553(3):2002;249-260
9. Fernandez-Checa J.C., et al. Oxidative stress: role of mitochondria and protection by glutathione. Biofactors. 8(1-2):1998;7-11
10. Coll O., et al. Sensitivity of the 2-oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion. Hepatology. 38(3):2003;692-702
11. Calabrese V., et al. Mitochondrial involvement in brain function and dysfunction: relevance to aging, neurodegenerative disorders and longevity. Neurochem Res. 26(6):2001;739-764
12. Sastre J., Pallardo F.V., Vina J. The role of mitochondrial oxidative stress in aging. Free Radic Biol Med. 35(1):2003;1-8
13. Ames B.N. Delaying the mitochondrial decay of aging-a metabolic tune-up. Alzheimer Dis Assoc Disord. 17(Suppl 2):2003;S54-S57
14. Atamna H., et al. Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging. Proc Natl Acad Sci USA. 99(23):2002;14807-14812
15. Ozawa T., et al. Quantitative determination of deleted mitochondrial DNA relative to normal DNA in parkinsonian striatum by a kinetic PCR analysis. Biochem Biophys Res Commun. 172(2):1990;483-489
16. Barja G. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr. 31(4):1999;347-366
17. Ruggiero F.M., et al. Lipid composition in synaptic and nonsynaptic mitochondria from rat brains and effect of aging. J Neurochem. 59(2):1992;487-491
18. Fridovich I. Fundamental aspects of reactive oxygen species, or what's the matter with oxygen? Ann N Y Acad Sci. 893:1999;13-18
19. Betteridge D.J. What is oxidative stress? Metabolism. 49(Suppl 1):2000;3-8
20. Halliwell B. Oxygen and nitrogen are pro-carcinogens. Damage to DNA by reactive oxygen, chlorine and nitrogen species: measurement, mechanism and the effects of nutrition. Mutat Res. 443(1-2):1999;37-52
21. Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr. 16:1996;33-50
22. Nordberg J., Arner E.S. Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med. 31(11):2001;1287-1312
23. Kuppusamy P., Zweier J.L. Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J Biol Chem. 264(17):1989;9880-9884
24. Kontos H.A., et al. Appearance of superoxide anion radical in cerebral extracellular space during increased prostaglandin synthesis in cats. Circ Res. 57(1):1985;142-151
25. McIntyre M., Bohr D.F., Dominiczak A.F. Endothelial function in hypertension: the role of superoxide anion. Hypertension. 34(Pt 1):1999;539-545
26. Babior B.M. NADPH oxidase: an update. Blood. 93(5):1999;1464-1476
27. Nauseef W.M. The NADPH-dependent oxidase of phagocytes. Proc Assoc Am Physicians. 111(5):1999;373-382
28. Thomas E.L., Lehrer R.I., Rest R.F. Human neutrophil antimicrobial activity. Rev Infect Dis. 10(Suppl 2):1988;S450-S456
29. Thannickal V.J., Fanburg B.L. Reactive oxygen species in cell signaling. Am J Physiol Lung Cell Mol Physiol. 279(6):2000;L1005-L1028
30. McCord J.M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 244(22):1969;6049-6055
31. Fridovich I. Superoxide anion radical (O2-.), superoxide dismutases, and related matters. J Biol Chem. 272(30):1997;18515-18517
32. Yost F.J. Jr., Fridovich I. An iron-containing superoxide dismutase from Escherichia coli. J Biol Chem. 248(14):1973;4905-4908
33. Chae H.Z., Kang S.W., Rhee S.G. Isoforms of mammalian peroxiredoxin that reduce peroxides in presence of thioredoxin. Methods Enzymol. 300:1999;219-226
34. Sundaresan M., et al. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science. 270(5234):1995;296-299
35. Choi H., et al. Structural basis of the redox switch in the OxyR transcription factor. Cell. 105(1):2001;103-113
36. Aslund F., et al. Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status. Proc Natl Acad Sci USA. 96(11):1999;6161-6165
37. Carmel-Harel O., et al. Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae. Mol Microbiol. 39(3):2001;595-605
38. Chen Y., Morrow J.D., Roberts L.J. 2nd Formation of reactive cyclopentenone compounds in vivo as products of the isoprostane pathway. J Biol Chem. 274(16):1999;10863-10868
39. Chae H.Z., et al. Characterization of three isoforms of mammalian peroxiredoxin that reduce peroxides in the presence of thioredoxin. Diabetes Res Clin Pract. 45(2-3):1999;101-112
40. Guerra A., et al. Acid phosphatase, genetic polymorphism and cardiovascular risk factors in a pediatric population. Rev Port Cardiol. 19(6):2000;679-691
41. Halliwell B. Oxidants and human disease: some new concepts. FASEB J. 1(5):1987;358-364
42. Halliwell B. Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res. 31(4):1999;261-272
43. Winterbourn C.C., Vissers M.C., Kettle A.J. Myeloperoxidase. Curr Opin Hematol. 7(1):2000;53-58
44. Rossi F., et al. Mechanism of production of toxic oxygen radicals by granulocytes and macrophages and their function in the inflammatory process. Pathol Res Pract. 180(2):1985;136-142
45. Mikkelsen R.B., Wardman P. Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms. Oncogene. 22(37):2003;5734-5754
46. Harris L.R., Cake M.H., Macey D.J. Iron release from ferritin and its sensitivity to superoxide ions differs among vertebrates. Biochem J. 301(Pt 2):1994;385-389
47. Balazy M., Nigam S. Aging, lipid modifications and phospholipases - new concepts. Ageing Res Rev. 2(2):2003;191-209
48. Drew B., Leeuwenburgh C. Aging and the role of reactive nitrogen species. Ann N Y Acad Sci. 959:2002;66-81
49. Kroncke K.D., Suschek C.V., Kolb-Bachofen V. Implications of inducible nitric oxide synthase expression and enzyme activity. Antioxid Redox Signal. 2(3):2000;585-605
50. Bredt D.S. Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic Res. 31(6):1999;577-596
51. Beck K.F., et al. Inducible NO synthase: role in cellular signalling. J Exp Biol. 202(Pt 6):1999;645-653
52. Andrew P.J., Mayer B. Enzymatic function of nitric oxide syntheses. Cardiovasc Res. 43(3):1999;521-531
53. Rubbo H., et al. Nitric oxide reaction with lipid peroxyl radicals spares alpha-tocopherol during lipid peroxidation. Greater oxidant protection from the pair nitric oxide/alpha-tocopherol than alpha-tocopherol/ascorbate. J Biol Chem. 275(15):2000;10812-10818
54. Hogg N., Kalyanaraman B. Nitric oxide and low-density lipoprotein oxidation. Free Radic Res. 28(6):1998;593-600
55. Ignarro L.J. Haem-dependent activation of guanylate cyclase and cyclic GMP formation by endogenous nitric oxide: a unique transduction mechanism for transcellular signaling. Pharmacol Toxicol. 67(1):1990;1-7
56. Liu J., Mori A.A. Age-associated changes in superoxide dismutase activity, thiobarbituric acid reactivity and reduced glutathione level in the brain and liver in senescence accelerated mice (SAM): a comparison with ddY mice. Mech Ageing Dev. 71(1-2):1993;23-30
57. Hussain S., Slikker W. Jr., Ali S.F. Age-related changes in antioxidant enzymes, superoxide dismutase, catalase, glutathione peroxidase and glutathione in different regions of mouse brain. Int J Dev Neurosci. 13(8):1995;811-817
58. Beckman J.S., Koppenol W.H. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol. 271(Pt 1):1996;C1424-C1437
59. van der Loo B., et al. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med. 192(12):2000;1731-1744
60. Imam S.Z., Ali S.F. Aging increases the susceptiblity to methamphetamine-induced dopaminergic neurotoxicity in rats: correlation with peroxynitrite production and hyperthermia. J Neurochem. 78(5):2001;952-959
61. Radi R., et al. Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys. 288(2):1991;481-487
62. Balazy M. Peroxynitrite and arachidonic acid. Identification of arachidonate epoxides. Pol J Pharmacol. 46(6):1994;593-600
63. O'Donnell V.B., et al. Nitration of unsaturated fatty acids by nitric oxide-derived reactive nitrogen species peroxynitrite, nitrous acid, nitrogen dioxide, and nitronium ion. Chem Res Toxicol. 12(1):1999;83-92
64. Meli R., et al. Reaction of peroxynitrite with carbon dioxide: intermediates and determination of the yield of CO3*- and NO2*. J Biol Inorg Chem. 7(1-2):2002;31-36
65. Goss S.P., Singh R.J., Kalyanaraman B. Bicarbonate enhances the peroxidase activity of Cu, Zn-superoxide dismutase. Role of carbonate anion radical. J Biol Chem. 274(40):1999;28233-28239
66. Singh R.J., et al. Nitration of gamma-tocopherol and oxidation of alpha-tocopherol by copper-zinc superoxide dismutase/H2O2/NO2-: role of nitrogen dioxide free radical. Proc Natl Acad Sci USA. 95(22):1998;12912-12917
67. Jiang H., et al. Nitrogen dioxide induces cis-trans-isomerization of arachidonic acid within cellular phospholipids. Detection of trans-arachidonic acids in vivo. J Biol Chem. 274(23):1999;16235-16241
68. Verma A., et al. Carbon monoxide: a putative neural messenger. Science. 259(5093):1993;381-384
69. Maines M.D. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 37:1997;517-554
70. Glaum S.R., Miller R.J. Zinc protoporphyrin-IX blocks the effects of metabotropic glutamate receptor activation in the rat nucleus tractus solitarii. Mol Pharmacol. 43(6):1993;965-969
71. White K.A., Marletta M.A. Nitric oxide synthase is a cytochrome P-450 type hemoprotein. Biochemistry. 31(29):1992;6627-6631
72. Foresti R., Motterlini R. The heme oxygenase pathway and its interaction with nitric oxide in the control of cellular homeostasis. Free Radic Res. 31(6):1999;459-475
73. Graser T., Vedernikov Y.P., Li D.S. Study on the mechanism of carbon monoxide induced endothelium-independent relaxation in porcine coronary artery and vein. Biomed Biochim Acta. 49(4):1990;293-296
74. Wang R., Wu L. Interaction of selective amino acid residues of K(ca) channels with carbon monoxide. Exp Biol Med (Maywood). 228(5):2003;474-480
75. Poon H.F., et al. Free radicals: key to brain aging and heme oxygenase as a cellular response to oxidative stress. J Gerontol. 2004;. in press
76. Drake J., et al. Elevation of brain glutathione by gamma-glutamylcysteine ethyl ester protects against peroxynitrite-induced oxidative stress. J Neurosci Res. 68(6):2002;776-784
77. Drake J., et al. Elevation of mitochondrial glutathione by gamma-glutamylcysteine ethyl ester protects mitochondria against peroxynitrite-induced oxidative stress. J Neurosci Res. 74(6):2003;917-927
78. Butterfield D., et al. Nutritional approaches to combat oxidative stress in Alzheimer's disease. J Nutr Biochem. 13(8):2002;444-461
79. Butterfield D.A., et al. Vitamin E and neurodegenerative disorders associated with oxidative stress. Nutr Neurosci. 5(4):2002;229-239
80. Calabrese V., et al. Disruption of thiol homeostasis and nitrosative stress in the cerebrospinal fluid of patients with active multiple sclerosis: evidence for a protective role of acetylcarnitine. Neurochem Res. 28(9):2003;1321-1328
81. Butterfield D.A., Pocernich C.B., Drake J. Elevated gutathione as a therapeutic strategy in Alzheimer's disease. Drug Dev Res. 56:2002;428-437
82. Droge W. Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol. 37(12):2002;1333-1345
83. Calabrese V., et al. Redox regulation of heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: a nutritional approach. Amino Acids. 25(3-4):2003;437-444
84. Calabrese V., et al. Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance. J Neurosci Res. 68(1):2002;65-75
85. Motterlini R., et al. Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med. 28(8):2000;1303-1312
86. Mayer R.J. From neurodegeneration to neurohomeostasis: the role of ubiquitin. Drug News Perspect. 16(2):2003;103-108
87. Calabrese V., et al. Molecular chaperones and their roles in neural cell differentiation. Dev Neurosci. 24(1):2002;1-13
88. Kelly S., Yenari M.A. Neuroprotection: heat shock proteins. Curr Med Res Opin. 18(Suppl 2):2002;S55-S60
89. Kelly S., et al. Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: influence of Bcl-2. Ann Neurol. 52(2):2002;160-167
90. Narasimhan P., et al. Astrocyte survival and HSP70 heat shock protein induction following heat shock and acidosis. Glia. 17(2):1996;147-159
91. Fink S.L., et al. Defective herpes simplex virus vectors expressing the rat brain stress-inducible heat shock protein 72 protect cultured neurons from severe heat shock. J Neurochem. 68(3):1997;961-969
92. Calabrese V., et al. Nitric oxide synthase induction in astroglial cell cultures: effect on heat shock protein 70 synthesis and oxidant/antioxidant balance. J Neurosci Res. 60(5):2000;613-622
93. Calabrese V., et al. HSP70 induction in the brain following ethanol administration in the rat: regulation by glutathione redox state. Biochem Biophys Res Commun. 269(2):2000;397-400
94. Scapagnini G., et al. Caffeic acid phenethyl ester and curcumin: a novel class of heme oxygenase-1 inducers. Mol Pharmacol. 61(3):2002;554-561
95. Sahlas D.J., Liberman A., Schipper H.M. Role of heme oxygenase-1 in the biogenesis of corpora amylacea. Biogerontology. 3(4):2002;223-231
96. Schipper H.M. Heme oxygenase-1: role in brain aging and neurodegeneration. Exp Gerontol. 35(6-7):2000;821-830
97. Goldbaum O., Richter-Landsberg C. Stress proteins in oligodendrocytes: differential effects of heat shock and oxidative stress. J Neurochem. 78(6):2001;1233-1242
98. Nath K.A., et al. The indispensability of heme oxygenase-1 in protecting against acute heme protein-induced toxicity in vivo. Am J Pathol. 156(5):2000;1527-1535
99. Bechtold D.A., Brown I.R. Induction of Hsp27 and Hsp32 stress proteins and vimentin in glial cells of the rat hippocampus following hyperthermia. Neurochem Res. 28(8):2003;1163-1173
100. Valentim L.M., et al. Changes in heat shock protein 27 phosphorylation and immunocontent in response to preconditioning to oxygen and glucose deprivation in organotypic hippocampal cultures. Neuroscience. 118(2):2003;379-386
101. Izaki K., et al. Induction of mitochondrial heat shock protein 60 and 10 mRNAs following transient focal cerebral ischemia in the rat. Brain Res Mol Brain Res. 88(1-2):2001;14-25
102. Turner C.P., Panter S.S., Sharp F.R. Anti-oxidants prevent focal rat brain injury as assessed by induction of heat shock proteins (HSP70, HO-1/HSP32, HSP47) following subarachnoid injections of lysed blood. Brain Res Mol Brain Res. 65(1):1999;87-102
103. Pocernich C.B., et al. Glutathione elevation and its protective role in acrolein-induced protein damage in synaptosomal membranes: relevance to brain lipid peroxidation in neurodegenerative disease. Neurochem Int. 39(2):2001;141-149
104. Pocernich C.B., La Fontaine M., Butterfield D.A. In-vivo glutathione elevation protects against hydroxyl free radical-induced protein oxidation in rat brain. Neurochem Int. 36(3):2000;185-191
105. Hammond C.L., Lee T.K., Ballatori N. Novel roles for glutathione in gene expression, cell death, and membrane transport of organic solutes. J Hepatol. 34(6):2001;946-954
106. Dringen R., Hirrlinger J. Glutathione pathways in the brain. Biol Chem. 384(4):2003;505-516
107. Frankel E.N. Chemistry of free radical and singlet oxidation of lipids. Prog Lipid Res. 23(4):1984;197-221
108. Halliwell B., Gutteridge J.M. Biologically relevant metal ion-dependent hydroxyl radical generation. An update. FEBS Lett. 307(1):1992;108-112
109. Spiteller G. Lipid peroxidation in aging and age-dependent diseases. Exp Gerontol. 36(9):2001;1425-1457
110. Esterbauer H., Schaur R.J., Zollner H. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 11(1):1991;81-128
111. Butterfield D.A., Stadtman E.R. Protein oxidation processes in aging brain. Adv Cell Aging Gerontol. 2:1997;161-191
112. Uchida K., Stadtman E.R. Modification of histidine residues in proteins by reaction with 4-hydroxynonenal. Proc Natl Acad Sci USA. 89(10):1992;4544-4548
113. Guichardant M., et al. Covalent modifications of aminophospholipids by 4-hydroxynonenal. Free Radic Biol Med. 25(9):1998;1049-1056
114. Pizzimenti S., et al. Inhibition of D1, D2, and A-cyclin expression in HL-60 cells by the lipid peroxydation product 4-hydroxynonenal. Free Radic Biol Med. 26(11-12):1999;1578-1586
115. Del Corso A., et al. Site-specific inactivation of aldose reductase by 4-hydroxynonenal. Arch Biochem Biophys. 350(2):1998;245-248
116. Boschi-Muller S., et al. A sulfenic acid enzyme intermediate is involved in the catalytic mechanism of peptide methionine sulfoxide reductase from Escherichia coli. J Biol Chem. 275(46):2000;35908-35913
117. Siems W.G., Hapner S.J., van Kuijk F.J. 4-hydroxynonenal inhibits Na(+)-K(+)-ATPase. Free Radic Biol Med. 20(2):1996;215-223
118. Butterfield D.A. Amyloid beta-peptide (1-42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer's disease brain. A review. Free Radic Res. 36(12):2002;1307-1313
119. Blanc E.M., et al. Amyloid beta-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells. J Neurochem. 68(5):1997;1870-1881
120. Uchida K., et al. Protein-bound acrolein: potential markers for oxidative stress. Proc Natl Acad Sci USA. 95(9):1998;4882-4887
121. Lovell M.A., Xie C., Markesbery W.R. Acrolein is increased in Alzheimer's disease brain and is toxic to primary hippocampal cultures. Neurobiol Aging. 22(2):2001;187-194
122. Lovell M.A., Xie C., Markesbery W.R. Acrolein, a product of lipid peroxidation, inhibits glucose and glutamate uptake in primary neuronal cultures. Free Radic Biol Med. 29(8):2000;714-720
123. Michiels C., Remacle J. Cytotoxicity of linoleic acid peroxide, malondialdehyde and 4-hydroxynonenal towards human fibroblasts. Toxicology. 66(2):1991;225-234
124. Esterbauer H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am J Clin Nutr. 57(Suppl 5):1993;779S-785S. discussion: 785S-6S
125. Basu A.K., Marnett L.J. Unequivocal demonstration that malondialdehyde is a mutagen. Carcinogenesis. 4(3):1983;331-333
126. Nair V., Offerman R.J., Turner G.A., Pryor A.N. Fluorescent 1, 4-dihydropyridines - the malondialdehyde connection. Tetrahedron. 44:1988;2793-2803
127. Agarwal S., Draper H.H. Isolation of a malondialdehyde-deoxyguanosine adduct from rat liver DNA. Free Radic Biol Med. 13(6):1992;695-699
128. Ji C., et al. Induction of cell cycle arrest by the endogenous product of lipid peroxidation, malondialdehyde. Carcinogenesis. 19(7):1998;1275-1283
129. King T.P. Selective chemical modification of arginyl residues. Biochemistry. 5(11):1966;3454-3459
130. Slatter D.A., et al. Reactions of lipid-derived malondialdehyde with collagen. J Biol Chem. 274(28):1999;19661-19669
131. Nair V., Vietti D.E., Cooper C.S. Degenerative chemistry of malondialdehyde. Structure, stereochemistry, and kinetics of formation of enaminals from reaction with amino acids. J Am Chem Soc. 103:1981;3030-3036
132. Slatter D.A., Murray M., Bailey A.J. Formation of a dihydropyridine derivative as a potential cross-link derived from malondialdehyde in physiological systems. FEBS Lett. 421(3):1998;180-184
133. Xu D., et al. Detection of circulating antibodies to malondialdehyde- acetaldehyde adducts in ethanol-fed rats. Gastroenterology. 115(3):1998;686-692
134. Slatter D.A., Bolton C.H., Bailey A.J. The importance of lipid-derived malondialdehyde in diabetes mellitus. Diabetologia. 43(5):2000;550-557
135. Fukunaga K., Yoshida M., Nakazono N. A simple, rapid, highly sensitive and reproducible quantification method for plasma malondialdehyde by high-performance liquid chromatography. Biomed Chromatogr. 12(5):1998;300-303
136. Wong S.H., et al. Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. Clin Chem. 33(Pt 1):1987;214-220
137. Young I.S., Trimble E.R. Measurement of malondialdehyde in plasma by high performance liquid chromatography with fluorimetric detection. Ann Clin Biochem. 28(Pt 5):1991;504-508
138. Morrow J.D., et al. Free radical-induced generation of isoprostanes in vivo. Evidence for the formation of D-ring and E-ring isoprostanes. J Biol Chem. 269(6):1994;4317-4326
139. Morrow J.D., et al. Nonenzymatic free radical-catalyzed generation of thromboxane-like compounds (isothromboxanes) in vivo. J Biol Chem. 271(38):1996;23185-23190
140. Taber D.F., Herr R.J., Gleave D.M. Diastereoselective synthesis of an isoprostane: (+/-)-8-epi-PGF(2)(alpha) ethyl ester. J Org Chem. 62(1):1997;194-198
141. Morrow J.D., Roberts L.J. The isoprostanes: unique bioactive products of lipid peroxidation. Prog Lipid Res. 36(1):1997;1-21
142. Brame C.J., et al. Identification of extremely reactive gamma-ketoaldehydes (isolevuglandins) as products of the isoprostane pathway and characterization of their lysyl protein adducts. J Biol Chem. 274(19):1999;13139-13146
143. Roberts L.J. 2nd, Morrow J.D. The generation and actions of isoprostanes. Biochim Biophys Acta. 1345(2):1997;121-135
144. Roberts L.J. 2nd, Reckelhoff J.F. Measurement of F(2)-isoprostanes unveils profound oxidative stress in aged rats. Biochem Biophys Res Commun. 287(1):2001;254-256
145. Roberts L.J., Morrow J.D. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med. 28(4):2000;505-513
146. Morrow J.D., et al. Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation. J Clin Invest. 90(6):1992;2502-2507
147. Moore S.A., et al. Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). J Neurochem. 56(2):1991;518-524
148. Roberts L.J. 2nd, et al. Formation of isoprostane-like compounds (neuroprostanes) in vivo from docosahexaenoic acid. J Biol Chem. 273(22):1998;13605-13612
149. Bernoud-Hubac N., et al. Formation of highly reactive gamma-ketoaldehydes (neuroketals) as products of the neuroprostane pathway. J Biol Chem. 276(33):2001;30964-30970
150. Davies S.S., et al. Effects of reactive gamma-ketoaldehydes formed by the isoprostane pathway (isoketals) and cyclooxygenase pathway (levuglandins) on proteasome function. FASEB J. 16(7):2002;715-717
151. Granstrom E., Kindahl H. Radioimmunoassay of prostaglandins and thromboxanes. Adv Prostaglandin Thromboxane Res. 5:1978;119-210
152. Proudfoot J., et al. Measurement of urinary F(2)-isoprostanes as markers of in vivo lipid peroxidation - a comparison of enzyme immunoassay with gas chromatography/mass spectrometry. Anal Biochem. 272(2):1999;209-215
153. Morrow J.D., Roberts L.J. 2nd Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress. Methods Enzymol. 300:1999;3-12
154. Delsal J.L. Nouveau procede d'extraction des lipids du serum per le methylal. Applications aux, icrodpsages du chlesterol total, des phosphoaminolipides et des proteines [Novel procedure for the extraction of serum lipids with methanol. Applications to determination of total cholesterol, amino phospholipids, and proteins]. Bull Soc Chim Biol (Paris). 26:1944;99-105
155. Vitiello F., Zanetta J.P. Thin-layer chromatography of phospholipids. J Chromatogr. 166(2):1978;637-640
156. Hedegaard E., Jensen B. Nano-scale densitometric quantitation of phospholipids. J Chromatogr. 225(2):1981;450-454
157. Lanza E., Zyren J., Slover H.T. Fatty acid analysis on short glass capillary columns. J Agric Food Chem. 28(6):1980;1182-1186
158. Murphy E.J., et al. Acidic hydrolysis of plasmalogens followed by high-performance liquid chromatography. Lipids. 28(6):1993;565-568
159. Yoritaka A., et al. Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA. 93(7):1996;2696-2701
160. Papaioannou N., et al. Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques. Amyloid. 8(1):2001;11-21
161. Calingasan N.Y., et al. Oxidative stress is associated with region-specific neuronal death during thiamine deficiency. J Neuropathol Exp Neurol. 58(9):1999;946-958
162. Sayre L.M., et al. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. J Neurochem. 68(5):1997;2092-2097
163. Youssef J.A., et al. Age-independent, gray matter-localized, brain-enhanced oxidative stress in male Fischer 344 rats: brain levels of F(2)-isoprostanes and F(4)-neuroprostanes. Free Radic Biol Med. 34(12):2003;1631-1635
164. Lopez G.H., et al. Age-associated changes in the content and fatty acid composition of brain glycerophospholipids. Comp Biochem Physiol B Biochem Mol Biol. 112(2):1995;331-343
165. Schroeder F., Goetz I., Roberts E. Sex and age alter plasma membranes of cultured fibroblasts. Eur J Biochem. 142(1):1984;183-191
166. Giusto N.M., et al. Age-associated changes in central nervous system glycerolipid composition and metabolism. Neurochem Res. 27(11):2002;1513-1523
167. Ulmann L., et al. Brain and hippocampus fatty acid composition in phospholipid classes of aged-relative cognitive deficit rats. Prostaglandins Leukot Essent Fatty Acids. 64(3):2001;189-195
168. Palinski W., et al. Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. Arteriosclerosis. 10(3):1990;325-335
169. Dei R., et al. Lipid peroxidation and advanced glycation end products in the brain in normal aging and in Alzheimer's disease. Acta Neuropathol (Berl). 104(2):2002;113-122
170. Head E., et al. Oxidative damage increases with age in a canine model of human brain aging. J Neurochem. 82(2):2002;375-381
171. Cini M., Moretti A. Studies on lipid peroxidation and protein oxidation in the aging brain. Neurobiol Aging. 16(1):1995;53-57
172. Randerath K., et al. I-compounds-endogenous DNA markers of nutritional status, ageing, tumour promotion and carcinogenesis. IARC Sci Publ. (124):1993;157-165
173. Randerath K., Li D.H., Randerath E. Age-related DNA modifications (I-compounds): modulation by physiological and pathological processes. Mutat Res. 238(3):1990;245-253
174. Randerath K., et al. Age-dependent covalent DNA alterations (I-compounds) in rodent tissues: species, tissue and sex specificities. Mutat Res. 219(2):1989;121-133
175. Morrow J.D., et al. Comparison of formation of D2/E2-isoprostanes and F2-isoprostanes in vitro and in vivo - effects of oxygen tension and glutathione. Arch Biochem Biophys. 353(1):1998;160-171
176. Balazs L., Leon M. Evidence of an oxidative challenge in the Alzheimer's brain. Neurochem Res. 19(9):1994;1131-1137
177. Perry T.L., et al. Amino acids, glutathione, and glutathione transferase activity in the brains of patients with Alzheimer's disease. Ann Neurol. 21(4):1987;331-336
178. Montine T.J., et al. Cerebrospinal fluid F2-isoprostane levels are increased in Alzheimer's disease. Ann Neurol. 44(3):1998;410-413
179. Pratico D., Rokach J., Tangirala R.K. Brains of aged apolipoprotein E-deficient mice have increased levels of F2-isoprostanes, in vivo markers of lipid peroxidation. J Neurochem. 73(2):1999;736-741
180. Pratico D., et al. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci. 21(12):2001;4183-4187
181. Lynch M.A. Analysis of the mechanisms underlying the age-related impairment in long-term potentiation in the rat. Rev Neurosci. 9(3):1998;169-201
182. Gupta K.P., et al. Age-dependent covalent DNA alterations (I-compounds) in rat liver mitochondrial DNA. Mutat Res. 237(1):1990;17-27
183. Cai Q., Tian L., Wei H. Age-dependent increase of indigenous DNA adducts in rat brain is associated with a lipid peroxidation product. Exp Gerontol. 31(3):1996;373-385
184. Mooradian A.D., et al. Age-related changes in tissue content of malondialdehyde-modified proteins. Life Sci. 55(20):1994;1561-1566
185. Yamamoto S. Mammalian lipoxygenases: molecular structures and functions. Biochim Biophys Acta. 1128(2-3):1992;117-131
186. Spiteller G. Peroxidation of linoleic acid and its relation to aging and age dependent diseases. Mech Ageing Dev. 122(7):2001;617-657
187. Hazen S.L., Ford D.A., Gross R.W. Activation of a membrane-associated phospholipase A2 during rabbit myocardial ischemia which is highly selective for plasmalogen substrate. J Biol Chem. 266(9):1991;5629-5633
188. Parthasarathy S., et al. Essential role of phospholipase A2 activity in endothelial cell-induced modification of low density lipoprotein. Proc Natl Acad Sci USA. 82(9):1985;3000-3004
189. Sapirstein A., et al. Cytosolic phospholipase A2 (PLA2), but not secretory PLA2, potentiates hydrogen peroxide cytotoxicity in kidney epithelial cells. J Biol Chem. 271(35):1996;21505-21513
190. Golconda M.S., Ueda N., Shah S.V. Evidence suggesting that iron and calcium are interrelated in oxidant-induced DNA damage. Kidney Int. 44(6):1993;1228-1234
191. Levine R.L., Stadtman E.R. Oxidative modification of proteins during aging. Exp Gerontol. 36(9):2001;1495-1502
192. Butterfield D.A., Stadtman E.R. Protein oxidation processes in aging brain. Adv Cell Aging Gerontol. 2:1997;161-191
193. Stadtman E.R. Metal ion-catalyzed oxidation of proteins: biochemical mechanism and biological consequences. Free Radic Biol Med. 9(4):1990;315-325
194. Butterfield D.A., Lauderback C.M. Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid beta-peptide-associated free radical oxidative stress. Free Radic Biol Med. 32(11):2002;1050-1060
195. Butterfield D.A., Kanski J. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev. 122(9):2001;945-962
196. Althaus J.S., et al. LC-MS/MS detection of peroxynitrite-derived 3-nitrotyrosine in rat microvessels. Free Radic Biol Med. 29(11):2000;1085-1095
197. Koppal T., et al. Peroxynitrite-induced alterations in synaptosomal membrane proteins: insight into oxidative stress in Alzheimer's disease. J Neurochem. 72(1):1999;310-317
198. Hall N.C., et al. Ischemia/reperfusion-induced changes in membrane proteins and lipids of gerbil cortical synaptosomes. Neuroscience. 64(1):1995;81-89
199. Hall N.C., et al. Effect of 2-cyclohexene-1-one-induced glutathione diminution on ischemia/reperfusion-induced alterations in the physical state of brain synaptosomal membrane proteins and lipids. Neuroscience. 77(1):1997;283-290
200. Subramaniam R., et al. The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease. Neurochem Res. 23(11):1998;1403-1410
201. Hensley K., et al. Electron paramagnetic resonance investigations of free radical-induced alterations in neocortical synaptosomal membrane protein infrastructure. Free Radic Biol Med. 17(4):1994;321-331
202. Hensley K., et al. Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation. J Neurochem. 65(5):1995;2146-2156
203. Hensley K., et al. Membrane protein alterations in rodent erythrocytes and synaptosomes due to aging and hyperoxia. Biochim Biophys Acta. 1270(2-3):1995;203-206
204. Aksenov M.Y., et al. Oxidative modification of glutamine synthetase by amyloid beta peptide. Free Radic Res. 27(3):1997;267-281
205. Howard B.J., et al. Prevention of hyperoxia-induced alterations in synaptosomal membrane-associated proteins by N-tert-butyl-alpha-phenylnitrone and 4-hydroxy- 2, 2, 6, 6-tetramethylpiperidin-1-oxyl (Tempol). J Neurochem. 67(5):1996;2045-2050
206. Floyd R.A. Role of oxygen free radicals in carcinogenesis and brain ischemia. FASEB J. 4(9):1990;2587-2597
207. Smith C.D., et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and in Alzheimer disease. Proc Natl Acad Sci USA. 88(23):1991;10540-10543
208. Aksenova M.V., et al. Protein oxidation and enzyme activity decline in old Brown Norway rats are reduced by dietary restriction. Mech Ageing Dev. 100(2):1998;157-168
209. Dubey A., Forster M.J., Sohal R.S. Effect of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone on protein oxidation and life span. Arch Biochem Biophys. 324(2):1995;249-254
210. Cakatay U., et al. Relation of oxidative protein damage and nitrotyrosine levels in the aging rat brain. Exp Gerontol. 36(2):2001;221-229
211. Nicolle M.M., et al. Signatures of hippocampal oxidative stress in aged spatial learning-impaired rodents. Neuroscience. 107(3):2001;415-431
212. Butterfield D.A., et al. Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone. Proc Natl Acad Sci USA. 94(2):1997;674-678
213. Farr S.A., et al. The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem. 84(5):2003;1173-1183
214. Shin C.M., et al. Age-related changes in the distribution of nitrotyrosine in the cerebral cortex and hippocampus of rats. Brain Res. 931(2):2002;194-199
215. Tohgi H., et al. Alterations of 3-nitrotyrosine concentration in the cerebrospinal fluid during aging and in patients with Alzheimer's disease. Neurosci Lett. 269(1):1999;52-54
216. Sloane J.A., et al. Increased microglial activation and protein nitration in white matter of the aging monkey. Neurobiol Aging. 20(4):1999;395-405
217. Chung Y.H., et al. Immunohistochemical study on the distribution of nitrotyrosine and neuronal nitric oxide synthase in aged rat cerebellum. Brain Res. 951(2):2002;316-321
218. Agarwal S., Sohal R.S. Aging and proteolysis of oxidized proteins. Arch Biochem Biophys. 309(1):1994;24-28
219. Sitte N., et al. Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part II - aging of nondividing cells. FASEB J. 14(15):2000;2503-2510
220. Sitte N., et al. Protein oxidation and degradation during proliferative senescence of human MRC-5 fibroblasts. Free Radic Biol Med. 28(5):2000;701-708
221. Sitte N., et al. Protein oxidation and degradation during cellular senescence of human BJ fibroblasts: part I - effects of proliferative senescence. FASEB J. 14(15):2000;2495-2502
222. Conconi M., et al. Age-related decline of rat liver multicatalytic proteinase activity and protection from oxidative inactivation by heat-shock protein 90. Arch Biochem Biophys. 331(2):1996;232-240
223. Keller J.N., Hanni K.B., Markesbery W.R. Possible involvement of proteasome inhibition in aging: implications for oxidative stress. Mech Ageing Dev. 113(1):2000;61-70
224. Keller J.N., Huang F.F., Markesbery W.R. Decreased levels of proteasome activity and proteasome expression in aging spinal cord. Neuroscience. 98(1):2000;149-156
225. Keller J.N., Gee J., Ding Q. The proteasome in brain aging. Ageing Res Rev. 1(2):2002;279-293
226. Friguet B., Szweda L.I. Inhibition of the multicatalytic proteinase (proteasome) by 4-hydroxy-2-nonenal cross-linked protein. FEBS Lett. 405(1):1997;21-25
227. Grune T., et al. Peroxynitrite increases the degradation of aconitase and other cellular proteins by proteasome. J Biol Chem. 273(18):1998;10857-10862
228. Glockzin S., et al. Activation of the cell death program by nitric oxide involves inhibition of the proteasome. J Biol Chem. 274(28):1999;19581-19586
229. Carney J.M., et al. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha- phenylnitrone. Proc Natl Acad Sci USA. 88(9):1991;3633-3636
230. Floyd R.A., Hensley K. Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging. 23(5):2002;795-807
231. Gibson G.E., et al. Oxidative stress and a key metabolic enzyme in Alzheimer brains, cultured cells, and an animal model of chronic oxidative deficits. Ann N Y Acad Sci. 893:1999;79-94
232. Vitorica J., et al. Age-related quantitative changes in enzyme activities of rat brain. Neurochem Res. 6(2):1981;127-136
233. Deloulme J.C., et al. Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation. J Neurochem. 66(3):1996;936-945
234. Ferrante F., Amenta F. Enzyme histochemistry of the choroid plexus in old rats. Mech Ageing Dev. 41(1-2):1987;65-72
235. Agrawal A., et al. Permeability function related to cerebral microvessel enzymes during ageing in rats. Int J Dev Neurosci. 14(2):1996;87-91
236. Hrachovina V., Mourek J. [Lactate dehydrogenase and malate dehydrogenase activity in the glial and neuronal fractions of the brain tissue in rats of various ages]. Sb Lek. 92(2-3):1990;39-44
237. Mizuno Y., Ohta K. Regional distributions of thiobarbituric acid-reactive products, activities of enzymes regulating the metabolism of oxygen free radicals, and some of the related enzymes in adult and aged rat brains. J Neurochem. 46(5):1986;1344-1352
238. Sandhu S.K., Kaur G. Mitochondrial electron transport chain complexes in aging rat brain and lymphocytes. Biogerontology. 4(1):2003;19-29
239. Kocak H., Oner P., Oztas B. Comparison of the activities of Na(+), K(+)-ATPase in brains of rats at different ages. Gerontology. 48(5):2002;279-281
240. Gorini A., et al. ATPases enzyme activities during ageing in different types of somatic and synaptic plasma membranes from rat frontal cerebral cortex. Prog Neuropsychopharmacol Biol Psychiatry. 26(1):2002;81-90
241. Vohra B.P., Sharma S.P., Kansal V.K. Age-dependent variations in mitochondrial and cytosolic antioxidant enzymes and lipid peroxidation in different regions of central nervous system of guinea pigs. Indian J Biochem Biophys. 38(5):2001;321-326
242. Sandhu S.K., Kaur G. Alterations in oxidative stress scavenger system in aging rat brain and lymphocytes. Biogerontology. 3(3):2002;161-173
243. Tsay H.J., et al. Age-associated changes of superoxide dismutase and catalase activities in the rat brain. J Biomed Sci. 7(6):2000;466-474
244. Aksenov M.Y., et al. Protein oxidation in the brain in Alzheimer's disease. Neuroscience. 103(2):2001;373-383
245. Castegna A., et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Free Radic Biol Med. 33(4):2002;562-571
246. Castegna A., et al. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem. 82(6):2002;1524-1532
247. Chen W., et al. Proteomic comparison between human young and old brains by two-dimensional gel electrophoresis and identification of proteins. Int J Dev Neurosci. 21(4):2003;209-216
248. Chang J., et al. Comparative proteomics: characterization of a two-dimensional gel electrophoresis system to study the effect of aging on mitochondrial proteins. Mech Ageing Dev. 124(1):2003;33-41
249. Soreghan B.A., et al. High-throughput proteomic-based identification of oxidatively induced protein carbonylation in mouse brain. Pharm Res. 20(11):2003;1713-1720
250. Visala Rao D., et al. Influence of ageing, heat shock treatment and in vivo total antioxidant status on gene-expression profile and protein synthesis in human peripheral lymphocytes. Mech Ageing Dev. 124(1):2003;55-69
251. Dierick J.F., et al. Proteomics in experimental gerontology. Exp Gerontol. 37(5):2002;721-734
252. Cobon G.S., et al. The proteomics of ageing. Biogerontology. 3(1-2):2002;133-136
253. Schoneich C. Proteomics in gerontological research. Exp Gerontol. 38(5):2003;473-481
254. Service R.F. Proteomics. Public projects gear up to chart the protein landscape. Science. 302(5649):2003;1316-1318
255. Toda T. Proteome and proteomics for the research on protein alterations in aging. Ann N Y Acad Sci. 928:2001;71-78
256. Butterfield D.A., et al. Proteomics in Alzheimer's disease: insights into mechanisms of neurodegeneration. J Neurochem. 86:2003;1313-1327
257. Butterfield D.A. Proteomics: a new approach to investigate oxidative stress in Alzheimer's disease brain. Brain Res. 1000:2004;1-7
258. Tamarit J., Cabiscol E., Ros J. Identification of the major oxidatively damaged proteins in Escherichia coli cells exposed to oxidative stress. J Biol Chem. 273(5):1998;3027-3032
259. Cabiscol E., Tamarit J., Ros J. Oxidative stress in bacteria and protein damage by reactive oxygen species. Int Microbiol. 3(1):2000;3-8
260. Cabiscol E., et al. Oxidative stress promotes specific protein damage in Saccharomyces cerevisiae. J Biol Chem. 275(35):2000;27393-27398
261. Poon H.F., Castegna A., Farr S.A., Thongboonkerd V., Lynn B.C., Banks W.A., et al. Quantitive proteomics analysis of specific protein expression and oxidative modification in aged SAMP8 mice brain. Neuroscience. 2004;. in press
262. Kimpara T., et al. Increased bilirubins and their derivatives in cerebrospinal fluid in Alzheimer's disease. Neurobiol Aging. 21(4):2000;551-554
263. Ames B.N., Shigenaga M.K., Hagen T.M. Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 90(17):1993;7915-7922