Intercommunication between metal ions and amyloidogenic peptides or proteins in protein misfolding disorders

The aggregation and accumulation of amyloidogenic peptides and proteins are observed as pathological features in the brains of patients suffering from neurodegenerative disorders. Metal ions can affect their aggregation and cytotoxicity profiles through direct and indirect interactions. Therefore, gaining our greater understanding of the interactions between metal ions and amyloidogenic peptides and proteins would assist in elucidating the complicated pathological nature of neurodegenerative diseases and developing effective diagnostics and therapeutics. In this review, we illustrate metal-binding properties of amyloid-β (for Alzheimer's disease), tau (for Alzheimer's and Parkinson's diseases), prion protein (for Creutzfeldt-Jakob disease), and human islet amyloid polypeptide (for type 2 diabetes) and their aggregation behaviors in the presence of metal ions. Furthermore, we briefly describe oxidative modifications of amyloidogenic peptides and proteins triggered by metal ions with the consequent effects on their aggregation pathways.