Copper binding to PrP super(C) may inhibit prion disease propagation

• Published in: Brain research 2003-12, Vol.993 (1-2), p.192-200
• Main Authors: Hijazi, N, Shaked, Y, Rosenmann, H, Ben-Hur, T, Gabizon, R
• Format: Article
• Language: English
• ISSN: 0006-8993
• DOI: 10.1016/j.brainres.2003.09.014

Although it has been well established that PrP super(C), the normal isoform of PrP super(Sc), is a copper-binding protein, the role of this metal in the function of PrP super(C) as well as in prion disease pathology remains unclear. Here, we show that when scrapie-infected neuroblastoma cells were cultured in the presence of copper, the accumulation of PrP super(Sc) in these cells was markedly reduced. In addition, our results indicate that when normal neuroblastoma cells were cultured in the presence of copper ions, they could no longer bind and internalize PrP super(Sc). In another set of experiments, copper was added to the drinking water of normal and scrapie-infected hamsters. Our results show that administration of copper to normal hamsters induced cerebellar PrP super(C) accumulation. Most important, a significant delay in prion disease onset was observed when scrapie-infected hamsters were treated with copper. As shown before for neuroblastoma cells, also in vivo most of the copper-induced accumulation of PrP super(C) was intracellular. We hypothesized that PrP super(C) internalization by copper may hinder PrP super(Sc) interaction with this molecule, and thereby affect prion disease propagation.