Dissecting the copper bioinorganic chemistry of the functional and pathological roles of the prion protein: Relevance in Alzheimer's disease and cancer

The cellular prion protein (PrPC) is a metal-binding biomolecule that can interact with different protein partners involved in pivotal physiological processes, such as neurogenesis and neuronal plasticity. Recent studies profile copper and PrPC as important players in the pathological mechanisms of Alzheimer's disease and cancer. Although the copper-PrPC interaction has been characterized extensively, the role of the metal ion in the physiological and pathological roles of PrPC has been barely explored. In this article, we discuss how copper binding and proteolytic processing may impact the ability of PrPC to recruit protein partners for its functional roles. The importance to dissect the role of copper-PrPC interactions in health and disease is also underscored.