title: Disruption of Fibers from the Tau Model AcPHF6 by Naturally Occurring Aurones and Synthetic Analogues.
abstract: 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. Moreover, a tetrahydroxylated isomer, compound 24, was shown as a chemical probe of fibers 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.
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5250, Département de Chimie Moléculaire, 38041 Grenoble, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5063, Département de Pharmacochimie Moléculaire, 38400 St Martin d'Heres, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Lunven
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5250, Département de Chimie Moléculaire, 38041 Grenoble, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Bonnet
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5063, Département de Pharmacochimie Moléculaire, 38400 St Martin d'Heres, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Yahiaoui
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5063, Département de Pharmacochimie Moléculaire, 38400 St Martin d'Heres, France.
authors.forename: Wei
authors.initials: W
authors.lastname: Yi
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5063, Département de Pharmacochimie Moléculaire, 38400 St Martin d'Heres, France.
authors.forename: Laurène
authors.initials: L
authors.lastname: Da Costa
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5063, Département de Pharmacochimie Moléculaire, 38400 St Martin d'Heres, France.
authors.forename: Marine
authors.initials: M
authors.lastname: Peuchmaur
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5063, Département de Pharmacochimie Moléculaire, 38400 St Martin d'Heres, France.
authors.forename: Ahcène
authors.initials: A
authors.lastname: Boumendjel
authors.affiliation: Université Grenoble-Alpes , Grenoble F-38041, France.|Centre National de la Recherche Scientifique (CNRS), UMR 5250, Département de Chimie Moléculaire, 38041 Grenoble, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Chierici
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry*; D002942:Circular Dichroism / Q000379:methods; D005453:Fluorescence; D006801:Humans; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000378:metabolism*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D016875:tau Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001572:Benzofurans; D010455:Peptides; C486837:aurone; D016875:tau Proteins
keywords: AcPHF6; Alzheimer’s disease; Aurones; polyphenols; tau aggregation