Journal article
Cu(II) potentiation of Alzheimer aβ neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction
X Huang, MP Cuajungco, CS Atwood, MA Hartshorn, JDA Tyndall, GR Hanson, KC Stokes, M Leopold, G Multhaup, LE Goldstein, RC Scarpa, AJ Saunders, J Lim, RD Moir, C Glabe, EF Bowden, CL Masters, DP Fairlie, RE Tanzi, AI Bush
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 1999
Open access
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 H2O2 generation 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 cup..
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