The polyphenol altenusin inhibits in vitro fibrillization of tau and reduces induced tau pathology in primary neurons
Autor: | Sook Wern Chua, Amadeus Gladbach, Renee Whan, Alexander Macmillan, Michael Kassiou, Mercedes Cueto, Lev Lewis, Inmaculada Vaca, Janet van Eersel, Lars M. Ittner, Alberto Cornejo, Claire H. Stevens |
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Přispěvatelé: | National Health and Medical Research Council (Australia), Australian Research Council, Comisión Nacional de Investigación Científica y Tecnológica (Chile) |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Genetically modified mouse Tau pathology Physiology Cognitive Neuroscience Blotting Western Tau protein Microtubule associated protein tau Mice Transgenic tau Proteins Neuropathology In Vitro Techniques Microscopy Atomic Force Fibril Protein Aggregation Pathological Biochemistry Mice 03 medical and health sciences 0302 clinical medicine mental disorders Animals Humans Cells Cultured Neurons Antiaggregation biology Chemistry Biphenyl Compounds Neurofibrillary Tangles Cell Biology General Medicine Immunohistochemistry In vitro Disease Models Animal Neuroprotective Agents 030104 developmental biology Polyphenol biology.protein Biophysics Alzheimer’s disease 030217 neurology & neurosurgery Intracellular |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
Popis: | 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. This work has been funded by the National Health & Medical Research Council (NH&MRC 1037746, 1020562, 1083209) and the Australian Research Council (ARC 130102027) to L.M.I. A.C. was supported by Postdoctoral Fellowship CONICYT (74140034). L.M.I. is an NH&MRC Senior Research Fellow. |
Databáze: | OpenAIRE |
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