Prion disease, a neurodegenerative disorder, is widely believed to arise when a cellular prion protein (PrP(c)) undergoes conformational changes to a pathogenic isoform (PrP(Sc)). Recent data have shown PrP(c) to be copper binding and that it acquires antioxidant activity as a result. This enzymatic property is dependent mainly on copper binding to the octarepeats region. In normal human brain and human prion disease, there is a population of brain-derived PrP that has been truncated at the N-terminal which encompassed the octarepeats region. Increasing evidences have suggested imbalances of metal-catalyzed reactions to be the common denominator for several neurodegenerative diseases. Therefore, we propose that one of the causative factors for prion disease could be due to the imbalances in metal-catalyzed reactions resulting in an alteration of the antioxidant function. These result in an increase level of oxidative stress and, as such, trigger the neurodegenerative cascade. (C) 2000 Academic Press.
|Number of pages||4|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - Aug 28 2000|
- Oxidative stress
- Prion protein
- Superoxide dismutase