Copper and Zinc Binding to Amyloid-β: Coordination, Dynamics, Aggregation, Reactivity and Metal-Ion Transfer

The metal-ions copper, zinc and iron have been shown to be involved girl Alzheimer's disease (AD). Cu, Zn and Fe ions are proposed to be implicated in two key steps of AD pathology: 1) aggregation of the peptide amyloid-beta (A beta), and 2) production of reactive oxygen species (ROS) induced by A beta. There is compelling evidence that Cu and Zn bind directly. to A beta in AD. this formation of Cu/Zn-A beta complexes is thought to be aberrant as they have been detected only in AD, but not under healthy conditions. In this context, the understanding of how these metal ions interact with A beta, their influence on structure and oligomerization, become an important issue for AD. Moreover, the mechanism of ROS production by Cu-A beta in relation to its aggregations state, as well as the metal-transfer reaction from and to A beta are crucial in order to understand why A beta oligomers are highly toxic and why A beta seems to bind Cu and Zn only in AD.