Prion metal interaction: is prion pathogenesis a cause or a consequence of metal imbalance?

Functional role of cellular prion protein (PrPc) has been hypothesized to be in metal homeostasis and providing cells with a superoxide dismutase (SOD)-like activity to escape damage by reactive oxygen species (ROS). PrPc interacts with a range of divalent metal ions and undergoes Cu2+ as well as Zn2+-associated endocytosis, thereby maintaining homeostasis of these and other metal ions. Conformational change to a beta-sheet rich, protease resistant entity, reminiscent of the disease-associated scrapie form called PrPsc, has been found to be induced by interaction of PrPc with metal ions like Cu2+, Zn2+, Mn2+ and Fe2+.