Current concepts of excitotoxicity

Journal of Neuropathology and Experimental Neurology

Volumn 55, Issue 1, 1996, Pages 1-13

  Whetsell Jr , William O ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 AMINOPHENYL) 4 METHYL 7,8 METHYLENEDIOXY 5H 2,3 BENZODIAZEPINE; 2 AMINO 5 PHOSPHONOVALERIC ACID; 2 AMINO 7 PHOSPHONOHEPTANOIC ACID; 4 PHOSPHONOMETHYLPIPECOLIC ACID; 6 CYANO 7 NITRO 2,3 QUINOXALINEDIONE; 6 NITRO 7 SULFAMOYLBENZO[F]QUINOXALINE 2,3 DIONE; 6,7 DINITRO 2,3 QUINOXALINEDIONE; AMPA RECEPTOR; GLUTAMATE RECEPTOR; METABOTROPIC RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; RECEPTOR SUBUNIT;

BRAIN DISEASE; CELL MEMBRANE TRANSPORT; CELL METABOLISM; HUMAN; INTRACELLULAR TRANSPORT; ION TRANSPORT; NERVE CELL MEMBRANE POTENTIAL; NERVE CELL STIMULATION; NERVE DEGENERATION; NEUROTOXICITY; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN METABOLISM; PROTEIN SECRETION; RECEPTOR BINDING; REVIEW;

EID: 0030049066     PISSN: 00223069     EISSN: None     Source Type: Journal    
DOI: 10.1097/00005072-199601000-00001     Document Type: Review

References (127)

1. Olney JW. Brain lesions, obesity and other disturbances in mice treated with monosodium glutamate. Science 1969;164:719-21
2. Lucas DR, Newhouse JP. The toxic effect of sodium L-glutamate on the inner layers of the retina. AMA Arch Ophthal 1957;58: 193-201
3. Olney JW. Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL, eds. Kainic acid as a tool in neurobiology. New York: Raven Press, 1978:1-15
4. Watkins JC. Excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL, eds. Kainic acid as a tool in neurobiology. New York: Raven Press, 1978:37-69
5. Van Harreveld A. Compounds in brain extracts causing spreading depression of cerebral cortical activity and contraction of crustacean muscle. J Neurochem 1959;3:300-315
6. Cheung JY, Bonventre JV, Malis CD, Leaf A. Calcium and ischemic injury. N Engl J Med 1986;314:1670-76
7. MacDermott AB, Mayer ML, Westbrook GL, Smith SJ, Barker JL. NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurons. Nature 1986;321:519-22
8. Mayer ML, Westbrook GL. Permeation and block of N-methyl-D aspartic acid receptor channels by divalent cations in mouse cultured central neurons. J Physiol 1987;394:501-27
9. Choi DW. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988;1:623-34
10. Siesjo BK. Historical overview: Calcium, ischemia and death of brain cells Ann NY Acad Sci 1988;522:638-61
11. Meldrum B, Garthwaite J. Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol Sci 1990;11: 379-86
12. Scnwarcz R, Scholz D, Coyle JT. Structure-activity relations for the neurotoxicity of kainic acid derivatives and glutamate analogues Neuropharmacology 1978;17:145-51
13. Monaghan DR, Bridges RJ, Cotman CW. The excitatory amino acid receptors: Their classes, pharmacology and distinct properties in the function of the central nervous system. Ann Rev Pharmacol Toxicol 1989;29:365-402
14. Watkins JC, Krogsgaard-Larsen P, Honore T. Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci 1990;11:25-33
15. Whetsell WO, Shapira NA. Biology of disease: Neuroexcitation, excitotoxicity and human neurological disease. Laboratory Investigation 1993;68(4):372-87
16. Lodge D, Johnson KM. Noncompetitive excitatory amino acid receptor antagonists. Trends Pharmacol Sci 1990;11:81-86
17. Young AB, Fagg GE. Excitatory amino acid receptors in the brain: Membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci 1990;11:126-33
18. Sladeczek F, Pin JP, Recasens M, Bockaert J, Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 1985;317:717-19
19. Berridge MJ, Irvine RF. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 1985;312:231-315
20. Nishizuka Y. Turnover of inositol phospholipids and signal transduction. Science 1984;225:1365-70
21. Nicoletti F, Wroblewski JT, Novelli A, Alho H, Guidotti A, Costa E. The activation of inositol phospholipid metabolism as a signal-transducing system for excitatory amino acids in primary cultures of cerebellar granule cells. Journal of Neuroscience 1986;6(7): 1905-11
22. Sugiyama H, Ito I, Hirono C. A new type glutamate receptor linked to inositol phospholipid metabolism. Nature 1987;325:531-33
23. Conn PJ, Patel J, eds. The metabotropic glutamate receptors. Totowa, NJ: Humana Press, 1994:277
24. Verdoorn TA, Burnashev N, Monyer H, Seeburg PH, Sakmann B. Structural determinants of ion flow through recombinant glutamate receptor channels. Science 1991;252:1715-18
25. Sommer B, Kohler M, Sprengel R, Seeburg PH. RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 1991;67:11-19
26. Burnashev N, Monyer H, Seeburg PH, Sakmann B. Divalent ion permeability of AMPA receptor channels is dominated by edited form of a single subunit. Neuron 1992;8:189-98
27. Monyer H, Sprengel R, Schoepfer R, et al. Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Sci-ence 1992;256:1217-21
28. Hollmann M, O'Shea-Greenfield A, Rogers SW Heinemann S. Cloning by functional expression of a member of the glutamate receptor family. Nature 1989;342:643-48
29. Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S. Molecular cloning and characterization of the rat NMDA receptor. Nature 1991;354:31-37
30. Werner P, Voigt M, Keinanen K, Wisden W, Seeburg PH. Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature 1991;351:742-44
31. Nakanishi S. Molecular diversity of glutamate receptors and implications for brain function. Science 1992;258:597-602
32. Schoepp DD, Conn PJ. Metabotropic glutamate receptors in brain function and pathology. TiPS 1993;14:13-19
33. Conn PJ, Boss V, Chung DS. Second-messenger systems coupled to metabotropic glutamate receptors. In: Conn PJ, Patel J, eds. The metabotropic glutamate receptors. Totowa, NJ: Humana Press, 1994;3:59-98
34. 2+-like selective antagonism of excitatory amino acid-induced responses by α,∈-diaminopimelic acid, D-α-aminoadipate and HA-966 in isolated spinal cord of frog and immature rat. Brain Res 1978;148:536-42
35. Watkins JC, Olverman HJ. Agonists and antagonists for excitatory amino acid receptors. Trends Neurosci 1987;10(7):265-72
36. 3H]D-APS binding sites on brain membranes and anticonvulsant activity. Brain Res 1986;382:169-73
37. Lehman J, Chapman AG, Meldrum BS, Hutchison A, Tsai C, Wood PL. CGS 19755 is a potent and competitive antagonist at NMDA-type receptors. Eur J Pharmacol 1988;154:89-93
38. Lodge D, Anis NA. Effects of phencyclidine on excitatory amino acid activation of spinal interneurones in the cat Eur J Pharmacol 1982;77:203-4
39. Lodge D, Anis NA, Burton NR. Effects of optical isomers of ketamine on excitation of cat and rat spinal neurons by amino acids and acetylcholine. Neurosci Letters 1982;29:282-86
40. Wong EHF, Kemp JA, Priestley T. Knight AR, Woodruff GN, Iversen LL. The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist. PNAS 1986;83:7104-8
41. Choi DW, Viseskul V. Opioids and non-opioid enantiomers selectively attenuate N-methyl-D-aspartate neurotoxicity on cortical neurons. Eur J Pharmacol 1988;155:27-35
42. Davies J, Watkins JC. Depressant actions of γ-D-glutamylamino-methyl sulfonate (GAMS) on amino acid-induced and synaptic excitation in the cat spinal cord. Brain Res 1985;327:113-20
43. Honore T, Davies SN, Drejer J, et al. Quinoxalinediones: Potent competitive non-NMDA glutamate receptor antagonists. Science 1988;241:701-3
44. Kessler M, Baudry M, Lynch G. Quinoxaline derivatives are high-affinity antagonists of the NMDA receptor-associated glycine sites. Brain Res 1989;489:377-82
45. Sheardown MJ. Nielsen EO, Hansen AJ, Jacobsen P, Honore T. 2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline: A neuroprotectant for cerebral ischemia. Science 1990;247:571-74
46. Judge ME, Sheardown MJ, Jacobsen P, Honore T. Protection against post-ischemic behavioral pathology by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) in the gerbil. Neurosci Letters 1991;133:291-94
47. Donevan S, Rogawski M. GKI 52466, a 2,3-bensodiazepine, is a highly selective, noncompetitive antagonist of AMPA/kainate receptor responses. Neuron 1993;10:51-59
48. Seal AJ, Irving AJ, Henley JM, Collingridge GL. Stereoselective antagonism of the metabotropic glutamate receptor mGluR1 alpha by alpha-methyl-4-carboxyphenylglycine. Biochem Soc Trans 1994,22(2):138S
49. Rickard NS, Ng KT. Blockade of metabotropic glutamate receptors prevents long-term memory consolidation. Brain Res Bulletin 1995;36(4):355-59
50. Manzoni OJ, Weisskopf, MG, Nicoll RA. MCPG antagonizes metabotropic glutamate receptors but not long-term potentiation in the hippocampus. Europ J Neuroscience 1995;6(6):1050-54
51. Jane DE, Jones PL, Pook PC, Tse HW, Watkins JC. Actions of two new antagonists showing selectivity for different sub-types of metabotropic glutamate receptor in the neonatal rat spinal cord. Brit J Pharmacol 1994;112(3):809-16
52. Novelli A, Reilly JA, Lysko PG, Henneberry RC. Glutamate becomes neurotoxic via the N-methyl-D-aspartate receptor when intracellular energy levels are reduced. Brain Res 1988;451:205-12
53. Zeevalk GD, Nicklas WJ. Chemically induced hypoglycemia and anoxia: Relationship to glutamate receptor-mediated toxicity in retina. J Pharmacol Exp Ther 1990;253:1285-92
54. Zeevalk GD, Nicklas WJ. Mechanisms underlying initiation of excitotoxicity associated with metabolic inhibition. J Pharmacol Exp Ther 1991;257:870-78
55. Urbanska E, Ikonomidou C, Sieklucka M. Turski WA. Aminooxyacetic acid produces excitotoxic lesions in the rat striatum. Synapse 1991;9:129-35
56. McMastcr OG, Du F, French ED, Schwarcz R. Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: Evidence for mediation by NMDA receptors. Exp Neurol 1991;113:378-85
57. Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993;262:689-95
58. Beal MF, Swartz KJ, Hyman BT, Storey E, Finn SF, Koroshetz W. Aminooxyacetic acid results in excitotoxin lesions by a novel indirect mechanism. J Neurochem 1991;37:1068-73
59. Mecocci P, MacGarvey U, Kaufman AE, et al. Oxidative damage to mitochondrial DNA shows marked age-dependent increases in human brain. Ann Neurol 1993;34:609-16
60. Wallace DC, Shoffner JM, Trounce I, et al. Mitochondrial DNA mutations in human degenerative diseases and aging. Biochimica et Biophysica Acta 1995;1271:141-51
61. Auer RN, Siesjo BK Biological differences between ischemia, hypoglycemia and epilepsy. Ann Neurol 1988;24:699-707
62. Choi DW, Rothman SM. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Ann Rev Neurosci 1990;13:171-82
63. Hayes RL, Chapouris R, Lyeth BG, et al. Pretreatment with phencyclidine (PCP) attenuates long-term behavioral deficits following concussive brain injury in the rat. Neurosci Abst 1987;13:1254
64. Katayama Y, Cheun MK, Gorman L, Tamura T, Becker DP. Increase in extracellular glutamate and associated massive ionic fluxes following concussive brain injury. Neurosci Abst 1988;14. 1154
65. Brierley JB, Graham DI. Hypoxia and vascular disorders of the central nervous system. In: Greenfield's neuropathology, 4th ed. New York: Wiley and Sons, 1984:125-207
66. Perl TM, Bedard L, Kosatsky T, Hockin JC, Todd ECD, Remis RS. An outbreak of toxic encephalopathy caused by eating mussels contaminated with domoic acid. NEJM 1990;25:1775-80
67. Teitelbaum JS, Zatorre RJ, Carpenter S, et al. Neurologic sequelae of domoic acid intoxication due to the ingestion of contaminated mussels. NEJM 1990;25:1781-87
68. Cendes F, Andermann F, Carpenter S, Zatorre RJ, Cashman NR. Temporal lobe epilepsy caused by domoic acid intoxication: Evidence for glutamate receptor-mediated excitotoxicity in humans. Ann Neurol 1995;37:123-26
69. Du F, Whetsell WO, Abou-Khalil B, Blumenkopf B, Okuno R, Schwarcz R. Immunohistochemical study of quinolinic acid catabolism in epileptic human hippocampus. Soc Neurosci Abstr 1990;16:309
70. Schwarcz R, Ben-Ari Y, eds. Excitatory amino acids and epilepsy. In: Advances in experimental medicine and biology. New York: Plenum Press, 1986;203:734
71. Seisjo BK. Hypoglycemia, brain metabolism and brain damage. Diab Metabol Rev 1988;4:113-41
72. Wieloch T, Engelsen B, Westerberg E, Auer R. Lesions of the glutamatergic cortico-striatal projections in the rat ameliorate hypoglycemic brain damage in the striatum. Neuroscience Lett 1985;58:25-30
73. Sandberg MJ, Butcher SP, Hagberg H. Extracellular overflow of neuroactive amino acids during severe insulin-induced hypoglycemia: In vivo dialysis of the rat hippocampus. J Neurochem 1986;47:178-84
74. Wieloch T. Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist. Science 1985;230:681-83
75. Albin RL, Grenamyre JT. Alternative excitotoxic hypotheses. Neurology 1992;42:733-38
76. Coyle JT, Schwarcz R. Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature 1976;263:244-46
77. McGeer EG, McGeer PL. Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids. Nature 1976;263:517-19
78. Coyle JT, McGeer EG, McGeer PL, Schwarcz R. Neostriatal injections: A model for Huntington's Chorea In: McGeer EG, Olney JW, McGeer PL, eds. Kainic acid as a tool in neurobiology. New York: Raven Press, 1978:139-59
79. Olney JW, De Gubaroff T. Glutamate neurotoxicity and Huntington's Chorea. Nature 1978;271:557-59
80. Schwarcz R, Whetsell WO Jr, Mangano RM. Quinolinic acid: An endogenous metabolite that produces axon-sparing lesions in rat brain. Science 1983;219:316-18
81. Wolfensberger M, Amsler U, Cuenod M, Foster AC, Whetsell WO Jr, Schwarcz R. Identification of quinolinic acid in rat and human brain. Neuiosci Letter 1983;41:247-52
82. Foster AC, Whetsell WO Jr, Bird ED, Schwarcz R. Quinolinic acid phosphoribosyltransferase in human and rat brain: Activity in Huntington's disease and in quinolinate-lesioned rat striatum. Brain Res 1985;336:207-14
83. Schwarcz R, Okuno E, White RJ, Bird ED, Whetsell WO Jr. 3-hydroxyanthranilic acid oxygenase (3HAO) activity in Huntington's disease brain tissue. PNAS 1988;85:4079-81
84. Whetsell WO Jr, Schwarcz R. The organotypic tissue culture model of corticostriatal system used for examining amino acid neurotoxicity and its antagonism: Studies of kainic acid, quinolinic acid and (-)2-amino-7-phosphonoheptanoic acid. J Neural Trans Suppl 1983:53-63
85. Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB. Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 1986;321:168-71
86. Beal MF, Ferrante RJ, Swartz KJ, Kowall NW. Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. Neurosci 1991;11(6):1649-59
87. Whetsell WO Jr, Schwarcz R. Prolonged exposure to submicromolar concentrations of quinolinic acid causes excitotoxic damage in organotypic cultures of rat corticostriatal system. Neurosci Lett 1989;97:271-75
88. Jauch D, Urbanska EM, Guidetti P, et al. Dysfunction of brain kynurenic acid metabolism in Huntington's disease: Focus of kynurenine aminotransferases. J Neurol Sci 1995;130:39-47
89. Parker WD, Boyson SJ, Luder AS. Parks JK. Evidence for a defect in NADH: Ubiquinone oxidoreductase (complex I) in Huntington's disease. Neurology 1990;40:1231-34
90. Frim DM, Simpson J, Uhler TA, et al. Striatal degeneration induced by mitochondrial blockade is prevented by biologically delivered NGF. J Neurosci Res 1993;35:452-58
91. Schulz JB, Beal MF. Mitochondrial dysfunction in movement disorders. Current Opin in Neurol 1994;7:333-39
92. Schapira AHV, Cooper JM, Dexter D, et al. Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem 1990;54. 823-27
93. 1 reductase (complex I) deficiency in Parkinson's disease. J Neurochem 1990;55:2142-45
94. Storey E, Hyman BT, Jenkins B, et al. 1-methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism. J Neurochem 1992;58:1975-78
95. Beal MF. Does impairment of energy metabolism result in excitotoxic death in neurodegenerative illnesses? Ann Neurol 1992;13: 119-30
96. Turski L, Bressler K, Rettig KJ, Loschmann PA, Wachtel H. Protection of substantia nigra from MPP+ neurotoxicity by N-methyl-D-aspartate antagonists. Nature 1991;349:414-18
97. Loschmann PA, Lange KW, Wachtel H, Turski L. MPTP-induced degeneration: Interference with glutamate toxicity. J Neurol Transmission Suppl 1994;43:133-43
98. Difazio MC, Hollingsworth Z, Young AB, Penney JB. Glutamate receptors in the substantia nigra of Parkinson's disease brains. Neurology 1992;42:402-6
99. Plaitakis A, Nicklas WJ, Desnick RJ. Glutamate dehydrogenase deficiency in three patients with spinocerebellar syndrome. Ann Neurol 1980;7:297-303
100. Duvoisin RC, Chokroverty S, Lepore F, Nicklas WJ. Glutamate dehydrogenase deficiency in patients with olivopontocerebellar atrophy Neurology (Cleveland) 1983;33:1322-26
101. Yamaguchi T, Hayashi K, Murakami H, et al. Glutamate dehydrogenase deficiency in spinocerebellar degeneration. Neurochem Res 1982;7:627-36
102. Plaitakis A, Berl S, Yahr MD. Abnormal glutamate metabolism in adult-onset degenerative neurological disorder. Science 1982;216: 193-96
103. Plaitakis A, Berl S, Yahr MD. Neurological disorders associated with deficiency of glutamate dehydrogenase. Ann Neurol 1984;15: 144-53
104. Plaitakis A, Caroscio JT. Abnormal glutamate metabolism in amyotrophic lateral sclerosis. Ann Neurol 1987;22:575-79
105. Rothstein JD, Tsai G, Kuncl RW, et al. Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 1990;28:18-25
106. Battaglioli G, Martin DL, Plummer J, Messer A. Synaptosomal glutamate uptake declines progressively in the spinal cord of a mutant mouse with motor neuron disease. J Neurochem 1993;60: 1567-69
107. Krieger C, Wagey R, Lanius RA, et al. Activation of PKC reverses apparent NMDS receptor reduction in ALS. Neuro Rep 1993;4: 931-34
108. Rosen DR, Siddique T, Patterson D, et al. Mutations in Cu/Zn Superoxide dismutase gene are associated with familial amyotropic lateral sclerosis. Nature 1993;362:59-62
109. Beal MF. Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 1995;38:357-66
110. Rothstein JD, Bristol LA, Hosler B, Brown RH, Kuncl RW. Chronic inhibition of Superoxide dismutase produces apoptotic death of spinal neurons. PNAS 1994;91:4155-59
111. Bowling AC, Schulz JB, Brown RH, Beal ME Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J Neurochem 1993;61:2322-25
112. Johnston MV, McKinney M, Coyle JT. Evidence for a cholinergic projection to neocortex from neurons in basal forebrain. PNAS 1979;76:5392-96
113. Coyle JT, Price DL, DeLong MR. Alzheimer's Disease: A disorder of cortical cholinergic innervation. Science 1983;219:1184-90
114. Arendash GW, Millard WJ, Dunn AJ, Meyer EW. Long-term neuropathological and neurochemical effects of nucleus basalis lesion in the rat Science 1987;238:952-56
115. Procter AW, Palmer AM, Francis PT, et al. Evidence of glutamatergic denervation and possible abnormal metabolism in Alzheimer's disease. J Neurochem 1988;50:790-802
116. 3H] glutamate binding. J Neurochem 1987;48:543-51
117. Mattson MP. Excitatory amino acids, growth factors and calcium: A teeter-totter model for neural plasticity and degeneration. In: Ben-Ari Y, ed. Amino acids and neuronal plasticity. Adv Exp Med Biol New York: Plenum Press, 1990;268:211-20
118. Mattson MP, Rychlik B. Comparison of rates of neuronal development and survival in human and rat cerebral cortical cell cultures. Mech Ageing Dev 1991;60:171-87
119. Cheng B, Mattson MP. NGF and bFGF protect rat hippocampal and human cortical neurons against hypoglycemic damage by stabilizing calcium homeostasis. Neuron 1991;7:1031-41
120. Mattson MP. Calcium and neuronal injury in Alzheimer's disease: Contributions of β-amyloid precursor protein mismetabolism, free radicals, and metabolic compromise. Ann NY Acad Sci 1994;747: 50-76
121. Parker WD, Parks J, Filley CM, Kleinschmidt-DeMasters BK. Electron transports chain defects in Alzheimer's disease brain. Neurology 1994;44:1090-96
122. Subbarao KV, Richardson JS, Ang LS. Autopsy samples of Alzheimer's cortex show increased peroxidation in vitro. J Neurochem 1990;55:342-5
123. Palmer AM, Burns MA. Selective increase in lipid peroxidation in inferior temporal cortex in Alzheimer's disease. Brain Res 1994;645:338-42
124. Mecocci P, MacGarvey U, Beal ME Oxidative damage to mitochondrial DNA is increased in Alzheimer's disease. Ann Neurol 1994;36:747-51
125. Smith CD, Carney JM, Starke-Reed PE, et al. Excess brain protein oxidation and enzyme dysfunction in normal aging and Alzheimer disease, PNAS 1991;88:10540-44
126. Strittmater WJ, Weisgraber KH, Huang DY, et al. Binding of human apolipoprotein E to synthetic amyloid peptide isoform-specific effects and implications for late-onset Alzheimer disease. PNAS 1993;90:8098-8102
127. Whetsell WO Jr, Shapira NA, Schwarcz R. Direct and indirect excitotoxicity in CNS neurodegeneration. Brain Pathology 1994;4: 335-36