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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March 2002
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Research Article|
February 22 2002
Metal imbalance and compromised antioxidant function are early changes in prion disease
Alana M. THACKRAY;
Alana M. THACKRAY
∗Centre for Veterinary Science, Madingley Road, University of Cambridge, Cambridge CB3 0ES, U.K.
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Robert KNIGHT;
Robert KNIGHT
†Department of Chemistry, University of Hull, Hull HU6 7RX, U.K.
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Stephen J. HASWELL;
Stephen J. HASWELL
†Department of Chemistry, University of Hull, Hull HU6 7RX, U.K.
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Raymond BUJDOSO;
Raymond BUJDOSO
∗Centre for Veterinary Science, Madingley Road, University of Cambridge, Cambridge CB3 0ES, U.K.
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David R. BROWN
David R. BROWN
1
‡Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
1To whom correspondence should be addressed (e-mail bssdrb@bath.ac.uk).
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Publisher: Portland Press Ltd
Received:
September 11 2001
Revision Received:
November 12 2001
Accepted:
December 12 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 362 (2): 253–258.
Article history
Received:
September 11 2001
Revision Received:
November 12 2001
Accepted:
December 12 2001
Citation
Alana M. THACKRAY, Robert KNIGHT, Stephen J. HASWELL, Raymond BUJDOSO, David R. BROWN; Metal imbalance and compromised antioxidant function are early changes in prion disease. Biochem J 1 March 2002; 362 (2): 253–258. doi: https://doi.org/10.1042/bj3620253
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