title: The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons.
abstract: In Alzheimer's disease, the microtubule-associated protein tau forms intracellular neurofibrillary tangles (NFTs). A critical step in the formation of NFTs is the conversion of soluble tau into insoluble filaments. Accordingly, a current therapeutic strategy in clinical trials is aimed at preventing tau aggregation. Here, we assessed altenusin, a bioactive polyphenolic compound, for its potential to inhibit tau aggregation. Altenusin inhibits aggregation of tau protein into paired helical filaments in vitro. This was associated with stabilization of tau dimers and other oligomers into globular structures as revealed by atomic force microscopy. Moreover, altenusin reduced tau phosphorylation in cells expressing pathogenic tau, and prevented neuritic tau pathology induced by incubation of primary neurons with tau fibrils. However, treatment of tau transgenic mice did not improve neuropathology and functional deficits. Taken together, altenusin prevents tau fibrillization in vitro and induced tau pathology in neurons.
authors.affiliation: Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Sook Wern
authors.initials: SW
authors.lastname: Chua
authors.affiliation: Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, UNSW Australia , Sydney, NSW 2052, Australia.|Faculty of Medicine, Medical Technology School, University Andrés Bello , Sazié 2315, Santiago, Chile.
authors.forename: Alberto
authors.initials: A
authors.lastname: Cornejo
authors.affiliation: Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Janet
authors.initials: J
authors.lastname: van Eersel
authors.affiliation: Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Claire H
authors.initials: CH
authors.lastname: Stevens
authors.affiliation: Department of Chemistry, Faculty of Science, University of Chile , Las Palmeras 3425, Ñuñoa, Santiago, Chile.
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Vaca
authors.affiliation: Institute for Natural Products and Agrobiology CSIC , 38206 La Laguna, Tenerife, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Cueto
authors.affiliation: School of Chemistry and Faculty of Health Sciences, University of Sydney , Sydney, NSW 2006, Australia.
authors.forename: Michael
authors.identifier: 0000-0002-6655-0529
authors.initials: M
authors.lastname: Kassiou
authors.affiliation: Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Amadeus
authors.initials: A
authors.lastname: Gladbach
authors.affiliation: Biomedical Imaging Facility, Mark Wainright Analytical Centre, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Alex
authors.initials: A
authors.lastname: Macmillan
authors.affiliation: Biomedical Imaging Facility, Mark Wainright Analytical Centre, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Lev
authors.identifier: 0000-0002-5469-5456
authors.initials: L
authors.lastname: Lewis
authors.affiliation: Biomedical Imaging Facility, Mark Wainright Analytical Centre, UNSW Australia , Sydney, NSW 2052, Australia.
authors.forename: Renee
authors.initials: R
authors.lastname: Whan
authors.affiliation: Dementia Research Unit, School of Medical Sciences, Faculty of Medicine, UNSW Australia , Sydney, NSW 2052, Australia.|Neuroscience Research Australia , Sydney, NSW 2031, Australia.
authors.forename: Lars M
authors.identifier: 0000-0001-6738-3825
authors.initials: LM
authors.lastname: Ittner
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D018625:Microscopy, Atomic Force; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D066263:Protein Aggregation, Pathological / Q000517:prevention & control*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D001713:Biphenyl Compounds; D018696:Neuroprotective Agents; D016875:tau Proteins; C095643:altenusin
keywords: Alzheimer’s disease; Microtubule associated protein tau; antiaggregation