Mutual interference of Cu and Zn ions in Alzheimer's disease: Perspectives at the molecular level

Abstract

While metal ions such as copper and zinc are essential in biology, they are also linked to several amyloid-related diseases, including Alzheimer's disease (AD). Zinc and copper can indeed modify the aggregation pathways of the amyloid-β (Aβ) peptide, the key component encountered in AD. In addition, the redox active copper ions do produce Reactive Oxygen Species (ROS) when bound to the Aβ peptide. While Cu(i) or Cu(ii) or Zn(ii) coordination to the Aβ has been extensively studied in the last ten years, characterization of hetero-bimetallic Aβ complexes is still scarce. This is also true for the metal induced Aβ aggregation and ROS production, for which studies on the mutual influence of the copper and zinc ions are currently appearing. Last but not least, zinc can strongly interfere in therapeutic approaches relying on copper detoxification. This will be exemplified with a biological lead, namely metallothioneins, and with synthetic ligands.