Disruption of Fibers from the Tau Model AcPHF6 by Naturally Occurring Aurones and Synthetic Analogues.

The formation of tau aggregates is strongly linked to the neurodegenerative process in tauopathies such as Alzheimer’s disease (AD). Yet only a few molecules have shown to efficiently prevent the in vitro formation of those aggregates, and the identification of such molecules is still an ongoing interest in a therapeutic context. Herein, we report the in vitro evaluation of a series of aurones against the fibrillation of the tau-derived hexapeptide AcPHF6 model. Using thioflavin T-based fluorescence assays, circular dichroism and atomic force microscopy, we showed that aurones are capable of efficiently interacting with the tau-derived hexapeptide. Importantly, this work reveals a significant activity observed for polyhydroxylated aurones. In particular, aurone 23 displayed an almost complete inhibition of fibers formation as shown by AFM at a peptide/inhibitor 1:1 ratio. It is similar to that observed for myricetin, a polyphenolic compound, well-known to prevent the in vitro elongation of tau fibers. Mor...