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Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction.

Authors
  • 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
Type
Published Article
Journal
The Journal of biological chemistry
Publication Date
Dec 24, 1999
Volume
274
Issue
52
Pages
37111–37116
Identifiers
PMID: 10601271
Source
Medline
License
Unknown

Abstract

Oxidative stress markers as well as high concentrations of copper are found in the vicinity of Abeta amyloid deposits in Alzheimer's disease. The neurotoxicity of Abeta in cell culture has been linked to H(2)O(2) generation by an unknown mechanism. We now report that Cu(II) markedly potentiates the neurotoxicity exhibited by Abeta in cell culture. The potentiation of toxicity is greatest for Abeta1-42 > Abeta1-40 >> mouse/rat Abeta1-40, corresponding to their relative capacities to reduce Cu(II) to Cu(I), form H(2)O(2) in cell-free assays and to exhibit amyloid pathology. The copper complex of Abeta1-42 has a highly positive formal reduction potential ( approximately +500-550 mV versus Ag/AgCl) characteristic of strongly reducing cuproproteins. These findings suggest that certain redox active metal ions may be important in exacerbating and perhaps facilitating Abeta-mediated oxidative damage in Alzheimer's disease.

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