DOI
10.1074/jbc.274.52.37111
Abstract
Oxidative stress markers as well as high concentrations of copper are found in the vicinity of Aβ amyloid deposits in Alzheimer's disease. The neurotoxicity of Aβ in cell culture has been linked to H2O2generation by an unknown mechanism. We now report that Cu(II) markedly potentiates the neurotoxicity exhibited by Aβ in cell culture. The potentiation of toxicity is greatest for Aβ1–42 > Aβ1–40 ≫ mouse/rat Aβ1–40, corresponding to their relative capacities to reduce Cu(II) to Cu(I), form H2O2 in cell-free assays and to exhibit amyloid pathology. The copper complex of Aβ1–42 has a highly positive formal reduction potential (≈+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 Aβ-mediated oxidative damage in Alzheimer's disease.
Document Type
Article
Publication Date
12-24-1999
Publisher Statement
Copyright © 1999, The American Society for Biochemistry and Molecular Biology, Inc.
DOI: https://doi.org/10.1074/jbc.274.52.37111
The definitive version is available at: https://www.jbc.org/article/S0021-9258(19)53067-8
Recommended Citation
X. Huang, C.S. Atwood, M.P. Cuajungco, M. A. Hartshorn, J. Tyndall, G.R. Hanson, K.C. Stokes, M.C. Leopold, G.M. Multhaup, L.E. Goldstein, R.C. Scarpa, A.J. Saunders, J. Lim, R.D. Moir, C. Glabe, E.F. Bowden, C.L. Masters, D.P. Fairlie, R.E. Tanzi, and A.I. Bush, “Cu(II) Potentiation of Alzheimer Aβ Neurotoxicity,” Journal of Biological Chemistry, 1999, 274(52), 37111-37116.
