title: Metal imbalance and compromised antioxidant function are early changes in prion disease.
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.
authors.affiliation: Centre for Veterinary Science, Madingley Road, University of Cambridge, Cambridge CB3 0ES, U.K.
authors.forename: Alana M
authors.initials: AM
authors.lastname: Thackray
authors.forename: Robert
authors.initials: R
authors.lastname: Knight
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Haswell
authors.forename: Raymond
authors.initials: R
authors.lastname: Bujdoso
authors.forename: David R
authors.initials: DR
authors.lastname: Brown
mesh_terms: 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
chemical_list: D000975:Antioxidants; D011328:Prions; D008345:Manganese; D003300:Copper; D013482:Superoxide Dismutase; D019286:Endopeptidase K