Metal binding sites in amyloid oligomers: Complexes and mechanisms

Neurodegenerative diseases constitute a worldwide health problem. Metal ions are essential for life, but they are also involved in several neurodegenerative mechanisms such as protein aggregation, free radical generation and oxidative stress. Here, we address the role of metal ions and their pathological mechanisms in common neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), diabetes type II and dialysis-related amyloidosis. In some diseases the metal ions accelerate the aggregation of the amyloids, whereas in others they inhibit it. In particular, we focus on amyloid heterogeneity and the consequent range of possible metal binding modes in amyloids, and the effects of metal ion binding. Together, this leads to an overview of the structural variability and the underlying mechanisms of oligomeric amyloids complexed with metal ions. Knowledge of the metal-amyloid interactions and understanding the mechanism of the metal-induced oligomerization in amyloids are important for effective drug design to prevent and alleviate aggregation.