Oxidative stress in Alzheimer disease: A possibility for prevention

Neuropharmacology

Volumn 59, Issue 4-5, 2010, Pages 290-294

  Bonda, David J ^a   Wang, Xinglong ^a   Perry, George ^a,b   Nunomura, Akihiko ^c   Tabaton, Massimo ^d   Zhu, Xiongwei ^a   Smith, Mark A ^a  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

^b UNIVERSITY OF TEXAS AT SAN ANTONIO   (United States)

^c UNIVERSITY OF YAMANASHI   (Japan)

^d UNIVERSITY OF GENOA   (Italy)

Author keywords

Alzheimer disease; Antioxidants; Coenzyme Q; Dimebon; Mitochondrial antioxidants; MitoQ; Oxidative stress; Reactive oxidative species

Indexed keywords

ALPHA TOCOPHEROL; AMYLOID BETA PROTEIN; ANTIOXIDANT; ASCORBIC ACID; CENTRAL NERVOUS SYSTEM AGENTS; LEVACECARNINE; MITOQ; REACTIVE OXYGEN METABOLITE; THIOCTIC ACID; UBIDECARENONE; UBIQUINONE DERIVATIVE; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; BRAIN DISEASE; CELL STRESS; CLINICAL TRIAL; COGNITIVE DEFECT; DISEASE PREDISPOSITION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG ACCUMULATION; DRUG PENETRATION; HUMAN; LIPID PEROXIDATION; LIVER INJURY; METABOLIC DISORDER; MITOCHONDRIAL DNA DISORDER; MITOCHONDRIAL RESPIRATION; NERVE CELL LESION; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROFIBRILLARY TANGLE; NEUROPROTECTION; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN LOCALIZATION; REVIEW; SYMPTOM;

ALZHEIMER DISEASE; ANIMALS; ANTIOXIDANTS; HUMANS; MITOCHONDRIA; OXIDATIVE STRESS; REACTIVE OXYGEN SPECIES; UBIQUINONE;

EID: 77955917442     PISSN: 00283908     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2010.04.005     Document Type: Review

References (93)

1. Aksenov M.Y., Tucker H.M., Nair P., Aksenova M.V., Butterfield D.A., Estus S., Markesbery W.R. The expression of key oxidative stress-handling genes in different brain regions in Alzheimer's disease. Journal of Molecular Neuroscience 1998, 11:151-164.
2. Aliev G., Seyidova D., Raina A.K., Obrenovich M.E., Neal M.L., Siedlak S.L., Lamb B.T., Vinters H., Lamanna J.C., Smith M.A., Perry G. Vascular hypoperfusion, mitochondria failure and oxidative stress in Alzheimer's disease. Proceedings of the Indian National Science Academy 2003, B69:209-238.
3. Aliev G., Smith M.A., Obrenovich M.E., de la Torre J.C., Perry G. Role of vascular hypoperfusion-induced oxidative stress and mitochondria failure in the pathogenesis of Azheimer disease. Neurotoxicity Research 2003, 5:491-504.
4. Aliev G., Liu J., Shenk J.C., Fischbach K., Pacheco G.J., Chen S.G., Obrenovich M.E., Ward W.F., Richardson A.G., Smith M.A., Gasimov E., Perry G., Ames B.N. Neuronal mitochondrial amelioration by feeding acetyl-L-carnitine and lipoic acid to aged rats. Journal of Cellular and Molecular Medicine 2009, 13:320-333.
5. Ames B.N., Liu J. Delaying the mitochondrial decay of aging with acetylcarnitine. Annals of the New York Academy of Sciences 2004, 1033:108-116.
6. Anderson A.J., Cummings B.J., Cotman C.W. Increased immunoreactivity for Jun- and Fos-related proteins in Alzheimer's disease: association with pathology. Experimental Neurology 1994, 125:286-295.
7. Atwood C.S., Moir R.D., Huang X., Scarpa R.C., Bacarra N.M., Romano D.M., Hartshorn M.A., Tanzi R.E., Bush A.I. Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis. Journal of Biological Chemistry 1998, 273:12817-12826.
8. Atwood C.S., Smith M.A., Martins R.N., Tanzi R.E., Roher A.E., Bush A.I., Perry G. Neuroinflammatory environments promote amyloid-β deposition and posttranslational modification. Neuroinflammation: Mechanisms and Management 2003, 249-266. Humana Press Inc., Totowa, New Jersey. P.L. Wood (Ed.).
9. Atzori C., Ghetti B., Piva R., Srinivasan A.N., Zolo P., Delisle M.B., Mirra S.S., Migheli A. Activation of the JNK/p38 pathway occurs in diseases characterized by tau protein pathology and is related to tau phosphorylation but not to apoptosis. Journal of Neuropathology and Experimental Neurology 2001, 60:1190-1197.
10. Ballenger J.F. Progress in the history of Alzheimer's disease: the importance of context. Journal of Alzheimer's Disease 2006, 9:5-13.
11. Beal M.F. Mitochondrial dysfunction and oxidative damage in Alzheimer's and Parkinson's diseases and coenzyme Q10 as a potential treatment. Journal of Bioenergetics and Biomembranes 2004, 36:381-386.
12. Behl C., Davis J., Cole G.M., Schubert D. Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochemical and Biophysical Research Communications 1992, 186:944-950.
13. Behl C., Davis J.B., Lesley R., Schubert D. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 1994, 77:817-827.
14. Bonda D.J., Lee H.P., Lee H.G., Perry G., Zhu X., Smith M.A. Novel therapeutics for Alzheimer's disease: an update. Current Opinion in Drug Discovery & Development 2010, 13:235-246.
15. Bonda D.J., Wang X., Perry G., Smith M.A., Zhu X. Mitochondrial dynamics in Alzheimer disease: opportunities for future treatment strategies. Drugs and Aging 2010, 27:1-12.
16. Bozyczko-Coyne D., O'Kane T.M., Wu Z.L., Dobrzanski P., Murthy S., Vaught J.L., Scott R.W. CEP-1347/KT-7515, an inhibitor of SAPK/JNK pathway activation, promotes survival and blocks multiple events associated with Abeta-induced cortical neuron apoptosis. Journal of Neurochemistry 2001, 77:849-863.
17. Burton G.W., Joyce A., Ingold K.U. First proof that vitamin E is major lipid-soluble, chain-breaking antioxidant in human blood plasma. Lancet 1982, 2:327.
18. Butterfield D.A., Hensley K., Harris M., Mattson M., Carney J. beta-Amyloid peptide free radical fragments initiate synaptosomal lipoperoxidation in a sequence-specific fashion: implications to Alzheimer's disease. Biochemical and Biophysical Research Communications 1994, 200:710-715.
19. Butterfield D.A., Drake J., Pocernich C., Castegna A. Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide. Trends in Molecular Medicine 2001, 7:548-554.
20. Butterfield D.A., Poon H.F., St Clair D., Keller J.N., Pierce W.M., Klein J.B., Markesbery W.R. Redox proteomics identification of oxidatively modified hippocampal proteins in mild cognitive impairment: insights into the development of Alzheimer's disease. Neurobiology of Disease 2006, 22:223-232.
21. Butterfield D.A., Reed T., Perluigi M., De Marco C., Coccia R., Cini C., Sultana R. Elevated protein-bound levels of the lipid peroxidation product, 4-hydroxy-2-nonenal, in brain from persons with mild cognitive impairment. Neuroscience Letters 2006, 397:170-173.
22. Castegna A., Aksenov M., Aksenova M., Thongboonkerd V., Klein J.B., Pierce W.M., Booze R., Markesbery W.R., Butterfield D.A. 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 Radical Biology and Medicine 2002, 33:562-571.
23. Castegna A., Aksenov M., Thongboonkerd V., Klein J.B., Pierce W.M., Booze R., Markesbery W.R., Butterfield D.A. Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. Journal of Neurochemistry 2002, 82:1524-1532.
24. Castegna A., Thongboonkerd V., Klein J.B., Lynn B., Markesbery W.R., Butterfield D.A. Proteomic identification of nitrated proteins in Alzheimer's disease brain. Journal of Neurochemistry 2003, 85:1394-1401.
25. Castellani R.J., Harris P.L., Sayre L.M., Fujii J., Taniguchi N., Vitek M.P., Founds H., Atwood C.S., Perry G., Smith M.A. Active glycation in neurofibrillary pathology of Alzheimer disease: N(epsilon)-(carboxymethyl) lysine and hexitol-lysine. Free Radical Biology and Medicine 2001, 31:175-180.
26. Castellani R.J., Lee H.G., Zhu X., Nunomura A., Perry G., Smith M.A. Neuropathology of Alzheimer disease: pathognomonic but not pathogenic. Acta Neuropathologica 2006, 111:503-509.
27. Castellani R.J., Moreira P.I., Liu G., Dobson J., Perry G., Smith M.A., Zhu X. Iron: the redox-active center of oxidative stress in Alzheimer disease. Neurochemical Research 2007, 32:1640-1645.
28. Colton C.A., Gilbert D.L. Production of superoxide anions by a CNS macrophage, the microglia. FEBS Letters 1987, 223:284-288.
29. Cras P., Kawai M., Siedlak S., Mulvihill P., Gambetti P., Lowery D., Gonzalez-DeWhitt P., Greenberg B., Perry G. Neuronal and microglial involvement in beta-amyloid protein deposition in Alzheimer's disease. American Journal of Pathology 1990, 137:241-246.
30. Cuajungco M.P., Goldstein L.E., Nunomura A., Smith M.A., Lim J.T., Atwood C.S., Huang X., Farrag Y.W., Perry G., Bush A.I. Evidence that the beta-amyloid plaques of Alzheimer's disease represent the redox-silencing and entombment of abeta by zinc. Journal of Biological Chemistry 2000, 275:19439-19442.
31. Doody R.S., Gavrilova S.I., Sano M., Thomas R.G., Aisen P.S., Bachurin S.O., Seely L., Hung D. Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study. Lancet 2008, 372:207-215.
32. El Khoury J., Hickman S.E., Thomas C.A., Cao L., Silverstein S.C., Loike J.D. Scavenger receptor-mediated adhesion of microglia to beta-amyloid fibrils. Nature 1996, 382:716-719.
33. Good P.F., Werner P., Hsu A., Olanow C.W., Perl D.P. Evidence of neuronal oxidative damage in Alzheimer's disease. American Journal of Pathology 1996, 149:21-28.
34. Hayashi T., Shishido N., Nakayama K., Nunomura A., Smith M.A., Perry G., Nakamura M. Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-beta peptide. Free Radical Biology and Medicine 2007, 43:1552-1559.
35. Hensley K., Carney J.M., Mattson M.P., Aksenova M., Harris M., Wu J.F., Floyd R.A., Butterfield D.A. A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proceedings of the National Academy of Sciences of the United States of America 1994, 91:3270-3274.
36. Hirai K., Aliev G., Nunomura A., Fujioka H., Russell R.L., Atwood C.S., Johnson A.B., Kress Y., Vinters H.V., Tabaton M., Shimohama S., Cash A.D., Siedlak S.L., Harris P.L., Jones P.K., Petersen R.B., Perry G., Smith M.A. Mitochondrial abnormalities in Alzheimer's disease. Journal of Neuroscience 2001, 21:3017-3023.
37. Jellinger K.A. Clinicopathological analysis of dementia disorders in the elderly-an update. Journal of Alzheimer's Disease 2006, 9:61-70.
38. Katzman R. Alzheimer's disease. New England Journal of Medicine 1986, 314:964-973.
39. Keller J.N., Schmitt F.A., Scheff S.W., Ding Q., Chen Q., Butterfield D.A., Markesbery W.R. Evidence of increased oxidative damage in subjects with mild cognitive impairment. Neurology 2005, 64:1152-1156.
40. Kontush A., Berndt C., Weber W., Akopyan V., Arlt S., Schippling S., Beisiegel U. Amyloid-beta is an antioxidant for lipoproteins in cerebrospinal fluid and plasma. Free Radical Biology and Medicine 2001, 30:119-128.
41. Kwong L.K., Kamzalov S., Rebrin I., Bayne A.C., Jana C.K., Morris P., Forster M.J., Sohal R.S. Effects of coenzyme Q(10) administration on its tissue concentrations, mitochondrial oxidant generation, and oxidative stress in the rat. Free Radical Biology and Medicine 2002, 33:627-638.
42. Lass A., Forster M.J., Sohal R.S. Effects of coenzyme Q10 and alpha-tocopherol administration on their tissue levels in the mouse: elevation of mitochondrial alpha-tocopherol by coenzyme Q10. Free Radical Biology and Medicine 1999, 26:1375-1382.
43. Lee H.G., Casadesus G., Zhu X., Takeda A., Perry G., Smith M.A. Challenging the amyloid cascade hypothesis: senile plaques and amyloid-beta as protective adaptations to Alzheimer disease. Annals of the New York Academy of Sciences 2004, 1019:1-4.
44. Lee Y.J., Jeong S.Y., Karbowski M., Smith C.L., Youle R.J. Roles of the mammalian mitochondrial fission and fusion mediators Fis1, Drp1, and Opa1 in apoptosis. Molecular Biology of the Cell 2004, 15:5001-5011.
45. Lee H.G., Perry G., Moreira P.I., Garrett M.R., Liu Q., Zhu X., Takeda A., Nunomura A., Smith M.A. Tau phosphorylation in Alzheimer's disease: pathogen or protector?. Trends in Molecular Medicine 2005, 11:164-169.
46. Lee J., Boo J.H., Ryu H. The failure of mitochondria leads to neurodegeneration: do mitochondria need a jump start?. Adv Drug Deliv Rev 2009, 61:1316-1323.
47. Liu J., Atamna H., Kuratsune H., Ames B.N. Delaying brain mitochondrial decay and aging with mitochondrial antioxidants and metabolites. Annals of the New York Academy of Sciences 2002, 959:133-166.
48. Liu J., Head E., Gharib A.M., Yuan W., Ingersoll R.T., Hagen T.M., Cotman C.W., Ames B.N. 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. Proceedings of the National Academy of Sciences of the United States of America 2002, 99:2356-2361.
49. Liu J., Killilea D.W., Ames B.N. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L- carnitine and/or R-alpha -lipoic acid. Proceedings of the National Academy of Sciences of the United States of America 2002, 99:1876-1881.
50. Long J., Gao F., Tong L., Cotman C.W., Ames B.N., Liu J. Mitochondrial decay in the brains of old rats: ameliorating effect of alpha-lipoic acid and acetyl-L-carnitine. Neurochemical Research 2009, 34:755-763.
51. Lu C., Zhang D., Whiteman M., Armstrong J.S. Is antioxidant potential of the mitochondrial targeted ubiquinone derivative MitoQ conserved in cells lacking mtDNA?. Antioxidants & Redox Signaling 2008, 10:651-660.
52. Mark R.J., Lovell M.A., Markesbery W.R., Uchida K., Mattson M.P. A role for 4-hydroxynonenal, an aldehydic product of lipid peroxidation, in disruption of ion homeostasis and neuronal death induced by amyloid beta-peptide. Journal of Neurochemistry 1997, 68:255-264.
53. Milgram N.W., Araujo J.A., Hagen T.M., Treadwell B.V., Ames B.N. Acetyl-L-carnitine and alpha-lipoic acid supplementation of aged beagle dogs improves learning in two landmark discrimination tests. FASEB Journal 2007, 21:3756-3762.
54. Murphy M.P., Smith R.A. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annual Review of Pharmacology and Toxicology 2007, 47:629-656.
55. Murphy M.P. Development of lipophilic cations as therapies for disorders due to mitochondrial dysfunction. Expert Opin Biol Ther 2001, 1:753-764.
56. Nakamura M., Shishido N., Nunomura A., Smith M.A., Perry G., Hayashi Y., Nakayama K., Hayashi T. Three histidine residues of amyloid-beta peptide control the redox activity of copper and iron. Biochemistry 2007, 46:12737-12743.
57. Nunomura A., Perry G., Pappolla M.A., Wade R., Hirai K., Chiba S., Smith M.A. RNA oxidation is a prominent feature of vulnerable neurons in Alzheimer's disease. Journal of Neuroscience 1999, 19:1959-1964.
58. Nunomura A., Perry G., Pappolla M.A., Friedland R.P., Hirai K., Chiba S., Smith M.A. Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. Journal of Neuropathology and Experimental Neurology 2000, 59:1011-1017.
59. Nunomura A., Perry G., Aliev G., Hirai K., Takeda A., Balraj E.K., Jones P.K., Ghanbari H., Wataya T., Shimohama S., Chiba S., Atwood C.S., Petersen R.B., Smith M.A. Oxidative damage is the earliest event in Alzheimer disease. Journal of Neuropathology and Experimental Neurology 2001, 60:759-767.
60. Odetti P., Angelini G., Dapino D., Zaccheo D., Garibaldi S., Dagna-Bricarelli F., Piombo G., Perry G., Smith M., Traverso N., Tabaton M. Early glycoxidation damage in brains from Down's syndrome. Biochemical and Biophysical Research Communications 1998, 243:849-851.
61. Ogawa O., Zhu X., Perry G., Smith M.A. Mitochondrial abnormalities and oxidative imbalance in neurodegenerative disease. Science of Aging Knowledge Environment 2002, 2002:pe16.
62. Park K.W., Baik H.H., Jin B.K. IL-13-induced oxidative stress via microglial NADPH oxidase contributes to death of hippocampal neurons in vivo. Journal of Immunology 2009, 183:4666-4674.
63. Perrig W.J., Perrig P., Stahelin H.B. The relation between antioxidants and memory performance in the old and very old. Journal of the American Geriatrics Society 1997, 45:718-724.
64. Perry G., Smith M.A. Is oxidative damage central to the pathogenesis of Alzheimer disease?. Acta Neurologica Belgica 1998, 98:175-179.
65. Petersen R.B., Nunomura A., Lee H.G., Casadesus G., Perry G., Smith M.A., Zhu X. Signal transduction cascades associated with oxidative stress in Alzheimer's disease. Journal of Alzheimer's Disease 2007, 11:143-152.
66. Pratico D., Lee V.M.Y., Trojanowski J.Q., Rokach J., Fitzgerald G.A. Increased F2-isoprostanes in Alzheimer's disease: evidence for enhanced lipid peroxidation in vivo. FASEB Journal 1998, 12:1777-1783.
67. Pratico D., Clark C.M., Lee V.M., Trojanowski J.Q., Rokach J., FitzGerald G.A. Increased 8,12-iso-iPF2alpha-VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity. Annals of Neurology 2000, 48:809-812.
68. Pratico D., Uryu K., Leight S., Trojanoswki J.Q., Lee V.M. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. Journal of Neuroscience 2001, 21:4183-4187.
69. Pratico D., Clark C.M., Liun F., Rokach J., Lee V.Y., Trojanowski J.Q. Increase of brain oxidative stress in mild cognitive impairment: a possible predictor of Alzheimer disease. Archives of Neurology 2002, 59:972-976.
70. Rottkamp C.A., Raina A.K., Zhu X., Gaier E., Bush A.I., Atwood C.S., Chevion M., Perry G., Smith M.A. Redox-active iron mediates amyloid-beta toxicity. Free Radical Biology and Medicine 2001, 30:447-450.
71. Sayre L.M., Zagorski M.G., Surewicz W.K., Krafft G.A., Perry G. Mechanisms of neurotoxicity associated with amyloid beta deposition and the role of free radicals in the pathogenesis of Alzheimer's disease: a critical appraisal. Chemical Research in Toxicology 1997, 10:518-526.
72. Sayre L.M., Perry G., Harris P.L., Liu Y., Schubert K.A., Smith M.A. In situ oxidative catalysis by neurofibrillary tangles and senile plaques in Alzheimer's disease: a central role for bound transition metals. Journal of Neurochemistry 2000, 74:270-279.
73. Schipper H.M., Bennett D.A., Liberman A., Bienias J.L., Schneider J.A., Kelly J., Arvanitakis Z. Glial heme oxygenase-1 expression in Alzheimer disease and mild cognitive impairment. Neurobiology of Aging 2006, 27:252-261.
74. Smith M.A., Kutty R.K., Richey P.L., Yan S.D., Stern D., Chader G.J., Wiggert B., Petersen R.B., Perry G. Heme oxygenase-1 is associated with the neurofibrillary pathology of Alzheimer's disease. American Journal of Pathology 1994, 145:42-47.
75. Smith M.A., Taneda S., Richey P.L., Miyata S., Yan S.D., Stern D., Sayre L.M., Monnier V.M., Perry G. Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proceedings of the National Academy of Sciences of the United States of America 1994, 91:5710-5714.
76. Smith M.A., Richey Harris P.L., Sayre L.M., Beckman J.S., Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. Journal of Neuroscience 1997, 17:2653-2657.
77. Smith M.A., Hirai K., Hsiao K., Pappolla M.A., Harris P.L., Siedlak S.L., Tabaton M., Perry G. Amyloid-beta deposition in Alzheimer transgenic mice is associated with oxidative stress. Journal of Neurochemistry 1998, 70:2212-2215.
78. Smith M.A., Casadesus G., Joseph J.A., Perry G. Amyloid-beta and tau serve antioxidant functions in the aging and Alzheimer brain. Free Radical Biology and Medicine 2002, 33:1194-1199.
79. Smith R.A., Kelso G.F., James A.M., Murphy M.P. Targeting coenzyme Q derivatives to mitochondria. Methods in Enzymology 2004, 382:45-67.
80. Smith M.A., Zhu X., Tabaton M., Liu G., McKeel D.W., Cohen M.L., Wang X., Siedlak S.L., Dwyer B.E., Hayashi T., Nakamura M., Nunomura A., Perry G. Increased iron and free radical generation in preclinical Alzheimer disease and mild cognitive impairment. Journal of Alzheimer's Disease 2010, 19:363-372.
81. Tauskela J.S. MitoQ-a mitochondria-targeted antioxidant. IDrugs 2007, 10:399-412.
82. Wadsworth T.L., Bishop J.A., Pappu A.S., Woltjer R.L., Quinn J.F. Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease. Journal of Alzheimer's Disease 2008, 14:225-234.
83. Wang X., Su B., Fujioka H., Zhu X. Dynamin-like protein 1 reduction underlies mitochondrial morphology and distribution abnormalities in fibroblasts from sporadic Alzheimer's disease patients. American Journal of Pathology 2008, 173:470-482.
84. Wang X., Su B., Siedlak S.L., Moreira P.I., Fujioka H., Wang Y., Casadesus G., Zhu X. Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins. Proceedings of the National Academy of Sciences of the United States of America 2008, 105:19318-19323.
85. Wang X., Su B., Zheng L., Perry G., Smith M.A., Zhu X. The role of abnormal mitochondrial dynamics in the pathogenesis of Alzheimer's disease. Journal of Neurochemistry 2009, 109(Suppl. 1):153-159.
86. Yan S.D., Chen X., Schmidt A.M., Brett J., Godman G., Zou Y.S., Scott C.W., Caputo C., Frappier T., Smith M.A. Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proceedings of the National Academy of Sciences of the United States of America 1994, 91:7787-7791.
87. Yan S.D., Yan S.F., Chen X., Fu J., Chen M., Kuppusamy P., Smith M.A., Perry G., Godman G.C., Nawroth P., et al. Non-enzymatically glycated tau in Alzheimer's disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid beta-peptide. Nature Medicine 1995, 1:693-699.
88. Yan S.D., Chen X., Fu J., Chen M., Zhu H., Roher A., Slattery T., Zhao L., Nagashima M., Morser J., Migheli A., Nawroth P., Stern D., Schmidt A.M. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 1996, 382:685-691.
89. Zandi P.P., Anthony J.C., Khachaturian A.S., Stone S.V., Gustafson D., Tschanz J.T., Norton M.C., Welsh-Bohmer K.A., Breitner J.C. Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County study. Archives of Neurology 2004, 61:82-88.
90. Zhu X., Castellani R.J., Takeda A., Nunomura A., Atwood C.S., Perry G., Smith M.A. Differential activation of neuronal ERK, JNK/SAPK and p38 in Alzheimer disease: the 'two hit' hypothesis. Mechanisms of Ageing and Development 2001, 123:39-46.
91. Zhu X., Raina A.K., Perry G., Smith M.A. Alzheimer's disease: the two-hit hypothesis. Lancet Neurology 2004, 3:219-226.
92. Zhu X., Perry G., Moreira P.I., Aliev G., Cash A.D., Hirai K., Smith V.A. Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease. Journal of Alzheimer's Disease 2006, 9:147-153.
93. Zhu X., Lee H.G., Perry G., Smith M.A. Alzheimer disease, the two-hit hypothesis: an update. Biochimica et Biophysica Acta 2007, 1772:494-502.