Artículo de revista
Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction
Fecha
2019Registro en:
ChemistryOpen, Volumen 8, Issue 5, 2019, Pages 554-559
21911363
10.1002/open.201800222
Autor
Areche, Carlos
Zapata, Francisca
González, Mathias
Díaz, Esteban
Montecinos, Rubén
Hernández, Marcos
Melo, Francisco
Cornejo, Alberto
Institución
Resumen
Tau protein is a natively unfolded protein whose primary role is to participate in axonal transport closely associated with microtubules. Neurodegenerative disorders including Alzheimer's disease and Tauopathies involved tau protein that is found hyperphosphorylated in vivo; then, tau is detached from microtubules to form toxic aggregates or oligomers, which have a deleterious effect on membranes, triggering an inflammatory response. Considering finding tau inhibitors, we isolated two compounds in the ethyl acetate extract from Xanthoria ectaneoides (Nyl.) Zahlbr; ergosterol peroxide (1) and a new anthraquinone (2). We established the structure through spectroscopic data and biogenic considerations, and we named it “2-hydroxy-3-((8-hydroxy-3-methoxy-6-methylanthraquinonyl)oxy)propanoic acid”. This new anthraquinone was evaluated as a tau inhibitor by ThT fluorescence, dot blot assays and total internal reflection fluorescence microscopy. Our results strongly suggest that this anthraquinone remodels soluble oligomers and diminishes β-sheet content. Moreover, through the fluorescence labeling of cysteine inside of the microtubule-binding domain (4R), we showed that this anthraquinone could reduce the oligomers progression by inhibiting cysteine interactions.