Disruption of fibres from the AcPHF6 tau model by naturally occurring aurones and synthetic analogs  
L. Lunven, H. Bonnet, S. Yahiaoui, L. Da Costa, M. Peuchmaur, A. Boumendjel, S. Chierici
ACS Chem. Neurosci. 2016, 7, 995-1003.
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. Herewith, we report the in vitro evaluation of a rationly chosen and naturally occurring compounds, namely 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 fibres formation as shown by AFM at the low 1:1 ratio, peptide/inhibitor which is similar to that observed for the myricetin, a polyphenolic compound well-known to inhibit tau fibres formation. Moreover, a tetrahydroxylated isomer, compound 24, was shown as a marker of fibres rather than an inhibitor. Consequently, these results highlight aurones as a new promising scaffold to interfere with tau aggregation for both treatment and diagnosis of AD.