Current understanding of metal-dependent amyloid-beta aggregation and toxicity

Abstract

The discovery of effective therapeutics targeting amyloid-beta (A beta) aggregates for Alzheimer's disease (AD) has been very challenging, which suggests its complicated etiology associated with multiple pathogenic elements. In AD-affected brains, highly concentrated metals, such as copper and zinc, are found in senile plaques mainly composed of A beta aggregates. These metal ions are coordinated to A beta and affect its aggregation and toxicity profiles. In this review, we illustrate the current view on molecular insights into the assembly of A beta peptides in the absence and presence of metal ions as well as the effect of metal ions on their toxicity.