The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons

Sook Wern Chua, Alberto Cornejo, Janet Van Eersel, Claire H. Stevens, Inmaculada Vaca, Mercedes Cueto, Michael Kassiou, Amadeus Gladbach, Alex Macmillan, Lev Lewis, Renee Whan, Lars M. Ittner

Resultado de la investigación: Contribución a una revistaArtículo

14 Citas (Scopus)

Resumen

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.

Idioma originalInglés
Páginas (desde-hasta)743-751
Número de páginas9
PublicaciónACS Chemical Neuroscience
Volumen8
N.º4
DOI
EstadoPublicada - 19 abr 2017

Áreas temáticas de ASJC Scopus

  • Fisiología
  • Bioquímica
  • Neurociencia cognitiva
  • Biología celular

Huella Profundice en los temas de investigación de 'The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons'. En conjunto forman una huella única.

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    Chua, S. W., Cornejo, A., Van Eersel, J., Stevens, C. H., Vaca, I., Cueto, M., Kassiou, M., Gladbach, A., Macmillan, A., Lewis, L., Whan, R., & Ittner, L. M. (2017). The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons. ACS Chemical Neuroscience, 8(4), 743-751. https://doi.org/10.1021/acschemneuro.6b00433