α-Synuclein and β-Amyloid form a Bridged Copper Complex

Abstract

The deposition of insoluble β-amyloid (Aβ) peptide into extracellular senile plaques is a pathological hallmark of Alzheimer’s disease. Fragmented α-synuclein (αSyn) and a relatively high concentration of Cu2+ ions are found within amyloid deposits. Both Aβ and αSyn bind Cu2+ with an apparent dissociation constant in the sub-nanomolar range at physiological pH, fuelling speculation that deleterious redox chemistry and metal-mediated protein misfolding may contribute to disease progression. Binary Cu(Aβ) and Cu(αSyn) complexes have been extensively studied, although the Cu2+ coordination of heterogeneous mixtures of Aβ and αSyn has yet to be characterised. This study used synthetic N-terminal..