Small molecule inhibitors of Aβ assembly

The Aβ peptide assembles into a variety of distinct types of structures in vitro and in the brain which have different biological consequences. Differential effects of inhibitory small molecules suggest that a sequential monomer - oligomer - fibril mechanism is overly simplistic and that soluble toxic oligomers and fibrils can be formed in common or separate pathways depending on the local environment. As a result, the effects of inhibitors are often assay-dependent because multiple pathways are operating. This review discusses strategies for teasing apart the intricate protein-protein interactions that result in Aβ assembly.