Oxidative processes in Alzheimer's disease:: the role of Aβ-metal interactions

被引:136
作者
Lynch, T
Cherny, RA
Bush, AI [1 ]
机构
[1] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia
[2] Mental Hlth Res Inst Victoria, Neuropathol Lab, Parkville, Vic 3052, Australia
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit,Lab Oxidat Biol, Charlestown, MA 02129 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA
关键词
amyloid beta; metals; oxidative stress; hydrogen peroxide; neurodegeneration; antioxidants; superoxide dismutase;
D O I
10.1016/S0531-5565(00)00112-1
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
Alzheimer's disease is characterized by signs of a major oxidative stress in the neocortex and the concomitant deposition of Amyloid beta (A beta). A beta is a metalloprotein that binds copper. and is electrochemically active. A beta converts molecular oxygen into hydrogen peroxide by reducing copper or iron, and this may lead to Fenton chemistry. Hydrogen peroxide is a freely permeable prooxidant that may be responsible for many of the oxidative adducts that form in the Alzheimer-affected brain. The electrochemical activity of various A beta species correlates with the peptides' neurotoxicity in cell culture, and participation in the neuropathology of Alzheimer's disease. These reactions present a novel target for Alzheimer therapeutics. (C) 2000 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:445 / 451
页数:7
相关论文
共 34 条
  • [1] Oxidation of cytosolic proteins and expression of creatine kinase BB in frontal lobe in different neurodegenerative disorders
    Aksenova, MV
    Aksenov, MY
    Payne, RM
    Trojanowski, JQ
    Schmidt, ML
    Carney, JM
    Butterfield, DA
    Markesbery, WR
    [J]. DEMENTIA AND GERIATRIC COGNITIVE DISORDERS, 1999, 10 (02) : 158 - 165
  • [2] Dramatic aggregation of Alzheimer Aβ by Cu(II) is induced by conditions representing physiological acidosis
    Atwood, CS
    Moir, RD
    Huang, XD
    Scarpa, RC
    Bacarra, NME
    Romano, DM
    Hartshorn, MK
    Tanzi, RE
    Bush, AI
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (21) : 12817 - 12826
  • [3] Atwood CS, 1999, MET IONS BIOL SYST, V36, P309
  • [4] ATWOOD CS, 2000, IN PRESS J NEUROCHEM
  • [5] HYDROGEN-PEROXIDE MEDIATES AMYLOID-BETA PROTEIN TOXICITY
    BEHL, C
    DAVIS, JB
    LESLEY, R
    SCHUBERT, D
    [J]. CELL, 1994, 77 (06) : 817 - 827
  • [6] beta-Amyloid toxicity in organotypic hippocampal cultures: Protection by EUK-8, a synthetic catalytic free radical scavenger
    Bruce, AJ
    Malfroy, B
    Baudry, M
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (06) : 2312 - 2316
  • [7] Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1
    Bruijn, LI
    Houseweart, MK
    Kato, S
    Anderson, KL
    Anderson, SD
    Ohama, E
    Reaume, AG
    Scott, RW
    Cleveland, DW
    [J]. SCIENCE, 1998, 281 (5384) : 1851 - 1854
  • [8] Bush A. I., 1999, Society for Neuroscience Abstracts, V25, P14
  • [9] RAPID INDUCTION OF ALZHEIMER A-BETA AMYLOID FORMATION BY ZINC
    BUSH, AI
    PETTINGELL, WH
    MULTHAUP, G
    PARADIS, MD
    VONSATTEL, JP
    GUSELLA, JF
    BEYREUTHER, K
    MASTERS, CL
    TANZI, RE
    [J]. SCIENCE, 1994, 265 (5177) : 1464 - 1467
  • [10] BUSH AI, 1993, J BIOL CHEM, V268, P16109