(Bio)chemical Strategies To Modulate Amyloid-β Self-Assembly

Amyloid plaques are one of the two hallmarks of Alzheimer's disease (AD). They consist mainly of fibrils made of self-assembled amyloid-beta (A beta) peptides. A beta is produced in healthy brains from proteolytic cleavage of the amyloid precursor protein. A beta aggregates, in particular smaller, soluble aggregates, are toxic to cells. Hence, modulating the self-assembly of A beta became a very active field of research, with the aim to reduce the amount of the toxic aggregates of A beta or to block their toxic action. A great variety of molecules, chemical and biological, are able to modify the aggregation of A beta. Here we give an overview of the different mechanistic ways to modulate A beta aggregation and on which step in the self-assembly molecules can interfere. We discuss the aggregation modulators according to different important parameters, including the type of interaction (weak interaction, coordination or covalent bonds), the importance of kinetics and thermodynamics, the size of the modulating molecules, and binding specificity.