Amyloids are ubiquitous protein aggregates sharing common internal structural features; they are present in all organisms, from prokaryotes to eukaryotes, where they play physiological or pathological roles. Importantly, amyloids, which are generated by aggregation of a range of distinct proteins, could be a key factor in a number of major human disorders, the so-called conformational diseases. Because all amyloids exhibit similar cross-β motifs, one may envisage that molecules capable of blocking the formation of β-sheet structures could abolish aggregation of all amyloid proteins, albeit with different efficacies. Herein, two different β-sheet blockers were tested against a selection of amyloidogenic proteins, encompassing all the major types of amyloid-based disorders. Analysis of their blocking efficiency, using a simple but contrasted cell-based screening procedure, unequivocally confirms that they indeed behave as aggregation pan-inhibitors. The significant inhibitory effects observed for these compounds against all tested amyloidogenic proteins could spur a broader biological evaluation of other known and new amyloid aggregation inhibitors to further determine the potential use of this class of compounds for the universal treatment of conformational diseases.
Keywords: Alzheimer’s; Amyloid; anti-amyloid drug; conformational diseases; drug discovery.