Artículos de revistas
The Polyphenol Altenusin Inhibits in Vitro Fibrillization of Tau and Reduces Induced Tau Pathology in Primary Neurons
Fecha
2017Registro en:
ACS Chemical Neuroscience, Volumen 8, Issue 4, 2018, Pages 743-751
19487193
10.1021/acschemneuro.6b00433
Autor
Chua, Sook Wern
Cornejo, Alberto
Van Eersel, Janet
Stevens, Claire H.
Vaca Cerezo, Inmaculada
Cueto, Mercedes
Kassiou, Michael
Gladbach, Amadeus
Macmillan, Alex
Lewis, Lev
Whan, Renee
Ittner, Lars M.
Institución
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.