Metal imbalance and compromised antioxidant function are early changes in prion disease.
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.
Thackray
Alana M
AM
Centre for Veterinary Science, Madingley Road, University of Cambridge, Cambridge CB3 0ES, U.K.
Knight
Robert
R
Haswell
Stephen J
SJ
Bujdoso
Raymond
R
Brown
David R
DR
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D019286:Endopeptidase K / Q000378:metabolism; D005260:Female; D008297:Male; D008345:Manganese / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000302:isolation & purification / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D011328:Prions; D008345:Manganese; D003300:Copper; D013482:Superoxide Dismutase; D019286:Endopeptidase K