Metal complexes that bind to the amyloid-β peptide of relevance to Alzheimer's disease

Alzheimer's disease (AD) is the most common form of dementia, and is a multi-faceted disease that is characterized by oxidative stress, metal-ion dysregulation, and the formation of intracellular neurofibrillary tangles of tau protein and extracellular amyloid-beta (A beta) aggregates. This review will focus on the interaction of metal complexes with the A beta peptide, and how these interactions can modify the peptide aggregation pathway, oxidative stress, and overall toxicity of the A beta peptide. While certain endogenous metal complexes such as heme can enhance toxicity, a large number of reports detail the potentially protective effect of discrete metal complexes in AD. These results will be discussed in the context of ligand design to target specific peptide residues for covalent binding, modulate peptide aggregation towards non-toxic species, and enhance blood brain barrier access. Additional features of metal complexes such as light-activated A beta binding, catalytic antioxidant activity, and peptidase activity will be detailed. (C) 2020 Elsevier B.V. All rights reserved.