Metal-Binding to Amyloid-β Peptide: Coordination, Aggregation, and Reactive Oxygen Species Production

Amyloid-plaques are a hallmark of Alzheimer's disease. They consist mainly of an aggregated peptide called amyloid-β. These plaques also accumulate high concentrations of metal ions, mainly Cu, Zn, and Fe. Cu and Zn directly bind to amyloid-β in vivo. This triggered a strong research activity in order to understand the biology and chemistry of the interaction between metal ions and amyloid-β. This includes also the chemical and biophysical aspects of the metal-amyloid-β complexes. The present article describes the coordination chemistry of the Cu(II), Cu(I), Zn(II), and Fe(II) complexes in terms of ligand spheres and affinities. Moreover, metal ions modulate the self-assembly of amyloid-β into amyloids, a central event in Alzheimer's disease. Attention was paid on the catalytic role of Cu-bound to amyloid-β, in particular in terms of the production of reactive oxygen species, which have been proposed to be involved in the disease progression. Recent mechanistic insights are described.