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Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction.

ABSTRACT: 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 ?-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.

SUBMITTER: Areche C

PROVIDER: S-EPMC6496470 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction.

Areche Carlos C Zapata Francisca F González Mathias M Díaz Esteban E Montecinos Rubén R Hernández Marcos M Melo Francisco F Cornejo Alberto A

ChemistryOpen 20190208 5

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 <i>in vivo</i>; 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 com ...[more]

PMID: 31065505

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Dataset Information

Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction.

Publications

Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction.

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