Strategies Employing Transition Metal Complexes to Modulate Amyloid-β Aggregation

Abstract

Aggregation of amyloid-beta (A beta) peptides is implicated in the development of Alzheimer's disease (AD), the most common type of dementia. Thus, numerous efforts to identify chemical tactics to control the aggregation pathways of A beta peptides have been made. Among them, transition metal complexes as a class of chemical modulators against A beta aggregation have been designed and utilized. Transition metal complexes are able to carry out a variety of chemistry with A beta peptides (e.g., coordination chemistry and oxidative and proteolytic reactions for peptide modifications) based on their tunable characteristics, including the oxidation state of and coordination geometry around the metal center. This Viewpoint illustrates three strategies employing transition metal complexes toward modulation of A beta aggregation pathways (i.e., oxidation and hydrolysis of A beta as well as coordination to A beta), along with some examples of such transition metal complexes. In addition, proposed mechanisms for three reactivities of transition metal complexes with A beta peptides are discussed. Our greater understanding of how transition metal complexes have been engineered and used for alteration of A beta aggregation could provide insight into the new discovery of chemical reagents against A beta peptides found in AD.