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. 2002 Feb 15;362(Pt 1):253–258. doi: 10.1042/0264-6021:3620253

Metal imbalance and compromised antioxidant function are early changes in prion disease.

Alana M Thackray 1, Robert Knight 1, Stephen J Haswell 1, Raymond Bujdoso 1, David R Brown 1
PMCID: PMC1222383  PMID: 11829763

Abstract

The prion protein (PrP) has been shown to bind copper. In the present study we have investigated whether prion disease in a mouse scrapie model resulted in modification of metal concentrations. We found changes in the levels of copper and manganese in the brains of scrapie-infected mice prior to the onset of clinical symptoms. Interestingly, we noted a major increase in blood manganese in the early stages of disease. Analysis of purified PrP from the brains of scrapie-infected mice also showed a reduction in copper binding to the protein and a proportional decrease in antioxidant activity between 30 and 60 days post-inoculation. We postulate that alterations in trace-element metabolism as a result of changes in metal binding to PrP are central to the pathological modifications in prion disease.

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Selected References

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