Extracellular copper ions regulate cellular prion protein (PrPC) expression and metabolism in neuronal cells

The physiological functions of cellular prion protein (PrPC) remain unclear. It has been demonstrated that PrPC is a copper binding protein and proposed that its functions could be strictly linked to copper metabolism and neuroprotection. The aim of this study was to clarify how extracellular copper modifies PrPC expression and metabolism in cultured neurones. We reported here that copper delivered at physiological concentrations significantly decreases PrPC mRNA expression in GN11 neurones. Moreover, copper increases the release of PrPc into the culture medium. These results indicate that extracellular copper strongly affects the amount of cellular PrP and might represent an interesting strategy to decrease the expression of PrPc in neurones and its conversion in the pathological isoform PrPSc. (C) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.