Inhibition of Protein Aggregation and Amyloid Formation by Small Molecules

Alzheimer’s disease is characterized by extracellular senile plaques made of β-amyloid (Aβ) protein. Thus far, drug after drug in human trials has failed to slow its progression. How compounds that reduce fibril formation and toxicity in cells bind to the Aβ toxic oligomers, is unknown. This account reviews recent drugs mainly targeting Aβ, how they were identified and summarizes their successes from in vitro and in vivo experiments and frequent failures in clinical trials. We then report recent in vitro and simulation results on how inhibitors interact with Aβ monomers and oligomers, highly desirable knowledge for predicting new efficient drugs. We conclude with a perspective on the future of the inhibition of amyloid formation by small molecules/peptides.