title: Oleuropein and derivatives from olives as Tau aggregation inhibitors.
abstract: Tau isoforms constitute a family of microtubule-associated proteins that are mainly expressed in neurons of the central nervous system. They promote the assembly of tubulin monomers into microtubules and modulate their stability, thus playing a key structural role in the distal portion of axons. In Alzheimer's disease and related tauopathies, Tau aggregation into fibrillary tangles contributes to intraneuronal and glial lesions. We report herein the ability of three natural phenolic derivatives obtained from olives and derived food products to prevent such Tau fibrillization in vitro, namely hydroxytyrosol, oleuropein, and oleuropein aglycone. The latter was found to be more active than the reference Tau aggregation inhibitor methylene blue on both wild-type and P301L Tau proteins, inhibiting fibrillization at low micromolar concentrations. These findings might provide further experimental support for the beneficial nutritional properties of olives and olive oil as well as a chemical scaffold for the development of new drugs aiming at neurodegenerative tauopathies.
authors.affiliation: Univ Lille Nord de France, F-59000 Lille, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Daccache
authors.forename: Cedric
authors.initials: C
authors.lastname: Lion
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sibille
authors.forename: Melanie
authors.initials: M
authors.lastname: Gerard
authors.forename: Christian
authors.initials: C
authors.lastname: Slomianny
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.forename: Philippe
authors.initials: P
authors.lastname: Cotelle
mesh_terms: D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids; D009682:Magnetic Resonance Spectroscopy; D046529:Microscopy, Electron, Transmission; D031658:Olea / Q000737:chemistry*; D011714:Pyrans / Q000494:pharmacology*; D016875:tau Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D057888:Iridoid Glucosides; D039823:Iridoids; D011714:Pyrans; D016875:tau Proteins; C002769:oleuropein