Oxidative stress signalling in Alzheimer's disease

Brain Research

Volumn 1000, Issue 1-2, 2004, Pages 32-39

  Zhu, Xiongwei ^a   Raina, Arun K ^a   Lee, Hyoung Gon ^a   Casadesus, Gemma ^a   Smith, Mark A ^a   Perry, George ^a  

^a CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

A ; A PP; AD; Alzheimer's disease; Amyloid ; Amyloid protein precursor; c Jun N terminal kinase; Heme oxygenase; HO; JNK; Mitochondria; Oxidative stress; Stress activated protein kinase; Transition metal

Indexed keywords

4 HYDROXYNONENAL; ADVANCED GLYCATION END PRODUCT RECEPTOR; ALPHA TOCOPHEROL; AMYLOID BETA PROTEIN; CATALASE; CYTOCHROME C OXIDASE; DNA FRAGMENT; FREE RADICAL; GLUCOSE TRANSPORTER; GLUTAMATE TRANSPORTER; HEAT SHOCK PROTEIN; HEME OXYGENASE 1; HYDROGEN PEROXIDE; IRON REGULATORY PROTEIN 1; IRON REGULATORY PROTEIN 2; OXOGLUTARATE DEHYDROGENASE; PEROXIREDOXIN; PYRUVATE DEHYDROGENASE COMPLEX; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; STRESS ACTIVATED PROTEIN KINASE; SUPEROXIDE; SUPEROXIDE DISMUTASE; TAU PROTEIN;

ALZHEIMER DISEASE; BRAIN METABOLISM; DNA REPAIR; DNA STRAND BREAKAGE; ENZYME ACTIVATION; ENZYME INDUCTION; ENZYME LOCALIZATION; GENE EXPRESSION; GLYCATION; HUMAN; IRON RESPONSIVE ELEMENT; LIPID PEROXIDATION; NERVE DEGENERATION; NEUROFIBRILLARY TANGLE; NEUROPATHOLOGY; NEUROTOXICITY; NONHUMAN; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEOMICS; REVIEW; SENILE PLAQUE; SIGNAL TRANSDUCTION; SYNAPTOSOME; UPREGULATION;

ALZHEIMER DISEASE; ANIMALS; HUMANS; OXIDATIVE STRESS; SIGNAL TRANSDUCTION;

EID: 1842453324     PISSN: 00068993     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.brainres.2004.01.012     Document Type: Review

References (90)

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. J. Mol. Neurosci. 11:1998;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 disease. Proc. Indian Natl. Sci. Acad. B69:2003;209-238.
3. Anderson A.J., Cummings B.J., Cotman C.W. Increased immunoreactivity for Jun- and Fos-related proteins in Alzheimer's disease: association with pathology. Exp. Neurol. 125:1994;286-295.
4. 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. J. Neuropathol. Exp. Neurol. 60:2001;1190-1197.
5. Behl C., Davis J., Cole G.M., Schubert D. Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem. Biophys. Res. Commun. 186:1992;944-950.
6. Behl C., Davis J.B., Lesley R., Schubert D. Hydrogen peroxide mediates amyloid beta protein toxicity. Cell. 77:1994;817-827.
7. 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. J. Neurochem. 77:2001;849-863.
8. 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 Mol. Med. 7:2001;548-554.
9. 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. J. Neurochem. 82:2002;1524-1532.
10. 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 Radic. Biol. Med. 33:2002;562-571.
11. 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. J. Neurochem. 85:2003;1394-1401.
12. 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 Radic. Biol. Med. 31:2001;175-180.
13. Chandrasekaran K., Giordano T., Brady D.R., Stoll J., Martin L.J., Rapoport S.I. Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease. Brain Res. Mol. Brain Res. 24:1994;336-340.
14. Colton C.A., Gilbert D.L. Production of superoxide anions by a CNS macrophage, the microglia. FEBS Lett. 223:1987;284-288.
15. Connor J.R., Snyder B.S., Arosio P., Loeffler D.A., LeWitt P. A quantitative analysis of isoferritins in select regions of aged, parkinsonian and Alzheimer's diseased brains. J. Neurochem. 65:1995;717-724.
16. Cottrell D.A., Blakely E.L., Johnson M.A., Ince P.G., Turnbull D.M. Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology. 57:2001;260-264.
17. Cras P., Smith M.A., Richey P.L., Siedlak S.L., Mulvihill P., Perry G. Extracellular neurofibrillary tangles reflect neuronal loss and provide further evidence of extensive protein cross-linking in Alzheimer disease. Acta Neuropathol. 89:1995;291-295.
18. Cross C.E., Halliwell B., Borish E.T., Pryor W.A., Ames B.N., Saul R.L., McCord J.M., Harman D. Oxygen radicals and human disease. Ann. Intern. Med. 107:1987;526-545.
19. Ferrer I., Blanco R., Carmona M., Puig B. Phosphorylated mitogen-activated protein kinase (MAPK/ERK-P), protein kinase of 38 kDa (p38-P), stress-activated protein kinase (SAPK/JNK-P), and calcium/calmodulin-dependent kinase II (CaM kinase II) are differentially expressed in tau deposits in neurons and glial cells in tauopathies. J. Neural Transm. 108:2001;1397-1415.
20. Gibson G.E., Sheu K.F., Blass J.P. Abnormalities of mitochondrial enzymes in Alzheimer disease. J. Neural Transm. 105:1998;855-870.
21. Good P.F., Perl D.P., Bierer L.M., Schmeidler J. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study. Ann. Neurol. 31:1992;286-292.
22. Good P.F., Werner P., Hsu A., Olanow C.W., Perl D.P. Evidence of neuronal oxidative damage in Alzheimer's disease. Am. J. Pathol. 149:1996;21-28.
23. Hartzler A.W., Zhu X., Siedlak S.L., Castellani R.J., Avila J., Perry G., Smith M.A. The p38 pathway is activated in Pick disease and progressive supranuclear palsy: a mechanistic link between mitogenic pathways, oxidative stress, and tau. Neurobiol. Aging. 23:2002;855-859.
24. Hensley K., Floyd R.A., Zheng N.Y., Nael R., Robinson K.A., Nguyen X., Pye Q.N., Stewart C.A., Geddes J., Markesbery W.R., Patel E., Johnson G.V., Bing G. p38 kinase is activated in the Alzheimer's disease brain. J. Neurochem. 72:1999;2053-2058.
25. Heslop K.E., Goss-Sampson M.A., Muller D.P., Curzon G. Serotonin metabolism and release in frontal cortex of rats on a vitamin E-deficient diet. J. Neurochem. 66:1996;860-864.
26. Huang X., Cuajungco M.P., Atwood C.S., Hartshorn M.A., Tyndall J.D., Hanson G.R., Stokes K.C., Leopold M., Multhaup G., Goldstein L.E., Scarpa R.C., Saunders A.J., Lim J., Moir R.D., Glabe C., Bowden E.F., Masters C.L., Fairlie D.P., Tanzi R.E., Bush A.I. Cu(II) potentiation of Alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J. Biol. Chem. 274:1999;37111-37116.
27. Jang J.H., Surh Y.J. Beta-Amyloid induces oxidative DNA damage and cell death through activation of c-Jun N terminal kinase. Ann. N. Y. Acad. Sci. 973:2002;228-236.
28. Keller J.N., Mark R.J., Bruce A.J., Blanc E., Rothstein J.D., Uchida K., Waeg G., Mattson M.P. 4-Hydroxynonenal, an aldehydic product of membrane lipid peroxidation, impairs glutamate transport and mitochondrial function in synaptosomes. Neuroscience. 80:1997;685-696.
29. Lee S.C., Zhao M.L., Hirano A., Dickson D.W. Inducible nitric oxide synthase immunoreactivity in the Alzheimer disease hippocampus: association with Hirano bodies, neurofibrillary tangles, and senile plaques. J. Neuropathol. Exp. Neurol. 58:1999;1163-1169.
30. Lockhart B.P., Benicourt C., Junien J.L., Privat A. Inhibitors of free radical formation fail to attenuate direct beta-amyloid25-35 peptide-mediated neurotoxicity in rat hippocampal cultures. J. Neurosci. Res. 39:1994;494-505.
31. Loeffler D.A., Connor J.R., Juneau P.L., Snyder B.S., Kanaley L., De Maggio A.J., Nguyen H., Brickman C.M., LeWitt P.A. Transferrin and iron in normal, Alzheimer's disease and Parkinson's disease brain regions. J. Neurochem. 65:1995;710-724.
32. 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. J. Neurochem. 68:1997;255-264.
33. Mark R.J., Pang Z., Geddes J.W., Uchida K., Mattson M.P. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation. J. Neurosci. 17:1997;1046-1054.
34. Markesbery W.R., Lovell M.A. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer's disease. Neurobiol. Aging. 19:1998;33-36.
35. Martins R.N., Harper C.G., Stokes G.B., Masters C.L. Increased cerebral glucose-6-phosphate dehydrogenase activity in Alzheimer's disease may reflect oxidative stress. J. Neurochem. 46:1986;1042-1045.
36. Maurer I., Zierz S., Moller H.J. A selective defect of cytochrome c oxidase is present in brain of Alzheimer disease patients. Neurobiol. Aging. 21:2000;455-462.
37. Mecocci P., MacGarvey U., Beal M.F. Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann. Neurol. 36:1994;747-751.
38. Mecocci P., Beal M.F., Cecchetti R., Polidori M.C., Cherubini A., Chionne F., Avellini L., Romano G., Senin U. Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain. Mol. Chem. Neuropathol. 31:1997;53-64.
39. Mielke K., Herdegen T. JNK and p38 stresskinases-degenerative effectors of signal-transduction-cascades in the nervous system. Prog. Neurobiol. 61:2000;45-60.
40. Morishima Y., Gotoh Y., Zieg J., Barrett T., Takano H., Flavell R., Davis R.J., Shirasaki Y., Greenberg M.E. Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J. Neurosci. 21:2001;7551-7560.
41. Morsch R., Simon W., Coleman P.D. Neurons may live for decades with neurofibrillary tangles. J. Neuropathol. Exp. Neurol. 58:1999;188-197.
42. Nagy Z., Esiri M.M., LeGris M., Matthews P.M. Mitochondrial enzyme expression in the hippocampus in relation to Alzheimer-type pathology. Acta Neuropathol. (Berl.). 97:1999;346-354.
43. 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. J. Neurosci. 19:1999;1959-1964.
44. 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. J. Neuropathol. Exp. Neurol. 59:2000;1011-1017.
45. 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. J. Neuropathol. Exp. Neurol. 60:2001;759-767.
46. Pappolla M.A., Omar R.A., Kim K.S., Robakis N.K. Immunohistochemical evidence of oxidative [corrected] stress in Alzheimer's disease. Am. J. Pathol. 140:1992;621-628.
47. Parker W.D. Jr., Parks J., Filley C.M., Kleinschmidt-DeMasters B.K. Electron transport chain defects in Alzheimer's disease brain. Neurology. 44:1994;1090-1096.
48. Parker W.D. Jr., Mahr N.J., Filley C.M., Parks J.K., Hughes D., Young D.A., Cullum C.M. Reduced platelet cytochrome c oxidase activity in Alzheimer's disease. Neurology. 44:1994;1086-1090.
49. Pei J.J., Braak E., Braak H., Grundke-Iqbal I., Iqbal K., Winblad B., Cowburn R.F. Localization of active forms of C-jun kinase (JNK) and p38 kinase in Alzheimer's disease brains at different stages of neurofibrillary degeneration. J. Alzheimer's Dis. 3:2001;41-48.
50. Pei J.J., Braak H., Winblad B., Cowburn R.F., Iqbal K., Grundke-Iqbal I. Up-regulation of mitogen-activated protein kinases ERK1/2 and MEK1/2 is associated with the progression of neurofibrillary degeneration in Alzheimer's disease. Brain Res. Mol. Brain Res. 109:2002;45-55.
51. Perez M., Cuadros R., Smith M.A., Perry G., Avila J. Phosphorylated, but not native, tau protein assembles following reaction with the lipid peroxidation product, 4-hydroxy-2-nonenal. FEBS Lett. 486:2000;270-274.
52. Perry G., Smith M.A. Is oxidative damage central to the pathogenesis of Alzheimer disease? Acta Neurol. Belg. 98:1998;175-179.
53. Perry G., Taddeo M.A., Nunomura A., Zhu X., Zenteno-Savin T., Drew K.L., Shimohama S., Avila J., Castellani R.J., Smith M.A. Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: beyond damage and response. Comp. Biochem. Physiol., Part C Pharmacol. Toxicol. 133:2002;507-513.
54. Perry G., Nunomura A., Hirai K., Zhu X., Perez M., Avila J., Castellani R.J., Atwood C.S., Aliev G., Sayre L.M., Takeda A., Smith M.A. Is oxidative damage the fundamental pathogenic mechanism of Alzheimer's and other neurodegenerative diseases? Free Radic. Biol. Med. 33:2002;1475-1479.
55. Perry G., Taddeo M.A., Petersen R.B., Castellani R.J., Harris P.L., Siedlak S.L., Cash A.D., Liu Q., Nunomura A., Atwood C.S., Smith M.A. Adventiously-bound redox active iron and copper are at the center of oxidative damage in Alzheimer disease. Biometals. 16:2003;77-81.
56. Pincro D.J., Hu J., Connor J.R. Alterations in the interaction between iron regulatory proteins and their iron responsive element in normal and Alzheimer's disease brains. Cell Mol. Biol. (Noisy-le-grand). 46:2000;761-776.
57. Praprotnik D., Smith M.A., Richey P.L., Vinters H.V., Perry G. Plasma membrane fragility in dystrophic neurites in senile plaques of Alzheimer's disease: an index of oxidative stress. Acta Neuropathol. 91:1996;1-5.
58. 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. J. Neurosci. 21:2001;4183-4187.
59. Premkumar D.R., Smith M.A., Richey P.L., Petersen R.B., Castellani R., Kutty R.K., Wiggert B., Perry G., Kalaria R.N. Induction of heme oxygenase-1 mRNA and protein in neocortex and cerebral vessels in Alzheimer's disease. J. Neurochem. 65:1995;1399-1402.
60. Renkawek K., Bosman G.J., de Jong W.W. Expression of small heat-shock protein hsp 27 in reactive gliosis in Alzheimer disease and other types of dementia. Acta Neuropathol. (Berl.). 87:1994;511-519.
61. 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 Radic. Biol. Med. 30:2001;447-450.
62. Russell R.L., Siedlak S.L., Raina A.K., Bautista J.M., Smith M.A., Perry G. Increased neuronal glucose-6-phosphate dehydrogenase and sulfhydryl levels indicate reductive compensation to oxidative stress in Alzheimer disease. Arch. Biochem. Biophys. 370:1999;236-239.
63. Sano M., Ernesto C., Thomas R.G., Klauber M.R., Schafer K., Grundman M., Woodbury P., Growdon J., Cotman C.W., Pfeiffer E., Schneider L.S., Thal L.J. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's disease cooperative study. N. Engl. J. Med. 336:1997;1216-1222.
64. Savage M.J., Lin Y.G., Ciallella J.R., Flood D.G., Scott R.W. Activation of c-Jun N-terminal kinase and p38 in an Alzheimer's disease model is associated with amyloid deposition. J. Neurosci. 22:2002;3376-3385.
65. Sayre L.M., Zelasko D.A., Harris P.L., Perry G., Salomon R.G., Smith M.A. 4-Hydroxynonenal-derived advanced lipid peroxidation end products are increased in Alzheimer's disease. J. Neurochem. 68:1997;2092-2097.
66. Shoji M., Iwakami N., Takeuchi S., Waragai M., Suzuki M., Kanazawa I., Lippa C.F., Ono S., Okazawa H. JNK activation is associated with intracellular beta-amyloid accumulation. Brain Res. Mol. Brain Res. 85:2000;221-233.
67. Smith M.A. Alzheimer disease. Int. Rev. Neurobiol. 42:1998;1-54.
68. 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. Proc. Natl. Acad. Sci. U. S. A. 91:1994;5710-5714.
69. 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. Am. J. Pathol. 145:1994;42-47.
70. Smith M.A., Sayre L.M., Monnier V.M., Perry G. Radical AGEing in Alzheimer's disease. Trends Neurosci. 18:1995;172-176.
71. Smith M.A., Perry G., Richey P.L., Sayre L.M., Anderson V.E., Beal M.F., Kowall N. Oxidative damage in Alzheimer's. Nature. 382:1996;120-121.
72. Smith M.A., Harris P.L., Sayre L.M., Perry G. Iron accumulation in Alzheimer disease is a source of redox-generated free radicals. Proc. Natl. Acad. Sci. U. S. A. 94:1997;9866-9868.
73. Smith M.A., Richey Harris P.L., Sayre L.M., Beckman J.S., Perry G. Widespread peroxynitrite-mediated damage in Alzheimer's disease. J. Neurosci. 17:1997;2653-2657.
74. Smith M.A., Wehr K., Harris P.L.R., Siedlak S.L., Connor J.R., Perry G. Abnormal localization of iron regulatory protein in Alzheimer's disease. Brain Res. 788:1998;232-236.
75. Stewart W.F., Kawas C., Corrada M., Metter E.J. Risk of Alzheimer's disease and duration of NSAID use. Neurology. 48:1997;626-632.
76. Suzuki Y.J., Forman H.J., Sevanian A. Oxidants as stimulators of signal transduction. Free Radic. Biol. Med. 22:1997;269-285.
77. Takeda A., Smith M.A., Avila J., Nunomura A., Siedlak S.L., Zhu X., Perry G., Sayre L.M. In Alzheimer's disease, heme oxygenase is coincident with Alz50, an epitope of tau induced by 4-hydroxy-2-nonenal modification. J. Neurochem. 75:2000;1234-1241.
78. Takeda A., Perry G., Abraham N.G., Dwyer B.E., Kutty R.K., Laitinen J.T., Petersen R.B., Smith M.A. Overexpression of heme oxygenase in neuronal cells, the possible interaction with tau. J. Biol. Chem. 275:2000;5395-5399.
79. Troy C.M., Rabacchi S.A., Xu Z., Maroney A.C., Connors T.J., Shelanski M.L., Greene L.A. Beta-Amyloid-induced neuronal apoptosis requires c-Jun N-terminal kinase activation. J. Neurochem. 77:2001;157-164.
80. 2, caspase-3, NF-kappaB, p53 and c-Jun. Neurotoxicology. 23:2002;351-365.
81. Vitek M.P., Bhattacharya K., Glendening J.M., Stopa E., Vlassara H., Bucala R., Manogue K., Cerami A. Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc. Natl. Acad. Sci. U. S. A. 91:1994;4766-4770.
82. Wataya T., Nunomura A., Smith M.A., Siedlak S.L., Harris P.L., Shimohama S., Szweda L.I., Kaminski M.A., Avila J., Price D.L., Cleveland D.W., Sayre L.M., Perry G. High molecular weight neurofilament proteins are physiological substrates of adduction by the lipid peroxidation product hydroxynonenal. J. Biol. Chem. 277:2002;4644-4648.
83. Wei W., Wang X., Kusiak J.W. Signaling events in amyloid beta-peptide-induced neuronal death and insulin-like growth factor I protection. J. Biol. Chem. 277:2002;17649-17656.
84. 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. Nat. Med. 1:1995;693-699.
85. 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. 382:1996;685-691.
86. Zhu X., Rottkamp C.A., Boux H., Takeda A., Perry G., Smith M.A. Activation of p38 kinase links tau phosphorylation, oxidative stress, and cell cycle-related events in Alzheimer disease. J. Neuropathol. Exp. Neurol. 59:2000;880-888.
87. Zhu X., Rottkamp C.A., Zevez K., Atwood C.S., Perry G., Smith M.A. Metal-mediated amyloid-beta toxicity acts through the activation of JNK/SAPK pathway in Alzheimer disease. Free Radic. Biol. Med. 31:2001;S65.
88. 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. Mech. Ageing Dev. 123:2001;39-46.
89. Zhu X., Raina A.K., Rottkamp C.A., Aliev G., Perry G., Boux H., Smith M.A. Activation and redistribution of c-Jun N-terminal kinase/stress activated protein kinase in degenerating neurons in Alzheimer's disease. J. Neurochem. 76:2001;435-441.
90. Zhu X., Lee H.-G., Perry G., Raina A.K., Smith M.A. The MAPK pathways in Alzheimer's Disease. NeuroSignals. 11:2002;270-281.