Copper-dependent functions for the prion protein.
Prion diseases such as bovine spongiform encephalopathy and Creutzfeldt-Jakob disease are fatal neurodegenerative diseases. These diseases are characterized by the conversion of a normal cellular protein, the prion protein, to an abnormal isoform that is thought to be responsible for both pathogenesis in the disease and the infectious nature of the disease agent. Understanding the biology and metabolism of the normal prion protein is therefore important for understanding the nature of these diseases. This review presents evidence for the normal function of the cellular prion protein, which appears to depend on its ability to bind copper (Cu). There is now considerable evidence that the prion protein is an antioxidant. Once the prion protein binds Cu, it may have an activity like that of a superoxide dismutase. Conversion of the prion protein to an abnormal isoform might lead to a loss of antioxidant protection that could be responsible for neurodegeneration in the disease.
Brown
David R
DR
Department of Biology and Biochemistry, University of Bath, UK. bssdrb@bath.ac.uk
Sassoon
Judyth
J
D000818:Animals; D003300:Copper / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018384:Oxidative Stress; D011328:Prions / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011487:Protein Conformation; D013482:Superoxide Dismutase / Q000378:metabolism
D011328:Prions; D003300:Copper; D013482:Superoxide Dismutase