Membrane Binding Strongly Affecting the Dopamine Reactivity Induced by Copper Prion and Copper/Amyloid-β (Aβ) Peptides. A Ternary Copper/Aβ/Prion Peptide Complex Stabilized and Solubilized in Sodium Dodecyl Sulfate Micelles.

The combination between dyshomeostatic levels of catecholamine neurotransmitters and redox-active metals such as copper and iron exacerbates the oxidative stress condition that typically affects neurodegenerative diseases. We report a comparative study of the oxidative reactivity of copper complexes with amyloid-β (Aβ) and the prion peptide fragment 76-114 (PrP), containing the high-affinity binding site, toward dopamine and 4-methylcatechol, in aqueous buffer and in sodium dodecyl sulfate micelles, as a model membrane environment. The competitive oxidative and covalent modifications undergone by the peptides were also evaluated. The high binding affinity of Cu/peptide to micelles and lipid membranes leads to a strong reduction (Aβ) and quenching (PrP) of the oxidative efficiency of the binary complexes and to a stabilization and redox silencing of the ternary complex Cu/Aβ/PrP, which is highly reactive in solution. The results improve our understanding of the pathological and protective effects associated with these complexes, depending on the physiological environment.