The rich electrochemistry and redox reactions of the copper sites in the cellular prion protein

► We review the structures and electrochemical properties of PrP-copper complexes. ► Electrochemical behavior depends strongly on the copper load in the prion protein. ► Disparate findings in the literature are linked to specific experimental protocols. ► Redox chemistry of PrP-copper is compared to that of other copper-amyloid species. This paper reviews recent electrochemical studies of the copper complexes of prion protein (PrP) and its related peptides, and correlates their redox behavior to chemical and biologically relevant reactions. Particular emphasis is placed on the difference in redox properties between copper in the octarepeat (OR) and the non-OR domains of PrP, as well as differences between the high and low copper occupancy states in the OR domain. Several discrepancies in the literature concerning these differences are discussed and reconciled. The PrP copper complexes, in comparison to copper complexes of other amyloidogenic proteins/peptides, display a more diverse and richer redox chemistry. The specific protocols and caveats that need to be considered in studying the electrochemistry and redox reactions of copper complexes of PrP, PrP-derived peptides, and other related amyloidogenic proteins are summarized.