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

Carlos Areche, Francisca Zapata, Mathias González, Esteban Díaz, Rubén Montecinos, Marcos Hernández, Francisco Melo, Alberto Cornejo

Resultado de la investigación: Article

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.

Idioma originalEnglish
PublicaciónChemistryOpen
DOI
EstadoPublished - 1 ene 2019

Huella dactilar

Anthraquinones
Oligomers
Cysteine
tau Proteins
Fluorescence
Intrinsically Disordered Proteins
Poisons
Fluorescence microscopy
Labeling
Assays
Membranes

ASJC Scopus subject areas

  • Chemistry(all)

Citar esto

Areche, Carlos ; Zapata, Francisca ; González, Mathias ; Díaz, Esteban ; Montecinos, Rubén ; Hernández, Marcos ; Melo, Francisco ; Cornejo, Alberto. / Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction. En: ChemistryOpen. 2019.
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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 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.",
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Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction. / Areche, Carlos; Zapata, Francisca; González, Mathias; Díaz, Esteban; Montecinos, Rubén; Hernández, Marcos; Melo, Francisco; Cornejo, Alberto.

En: ChemistryOpen, 01.01.2019.

Resultado de la investigación: Article

TY - JOUR

T1 - Anthraquinone Derivative Reduces Tau Oligomer Progression by Inhibiting Cysteine-Cysteine Interaction

AU - Areche, Carlos

AU - Zapata, Francisca

AU - González, Mathias

AU - Díaz, Esteban

AU - Montecinos, Rubén

AU - Hernández, Marcos

AU - Melo, Francisco

AU - Cornejo, Alberto

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

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