Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids

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dc.contributor.author Guru, Krishnakumar Viswanathan
dc.contributor.author Paul, Ashim
dc.contributor.author Segal, Daniel
dc.date.accessioned 2018-01-30T11:28:17Z
dc.date.available 2018-01-30T11:28:17Z
dc.date.issued 2018-01
dc.identifier.citation Guru KrishnaKumar, V.; Paul, Ashim and Segal, Daniel, "Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids", Scientific Reports, DOI: 10.1038/s41598-017-18443-2, vol. 8, no. 1, 8,Jan. 2018. en_US
dc.identifier.issn 2045-2322
dc.identifier.uri http://dx.doi.org/10.1038/s41598-017-18443-2
dc.identifier.uri https://repository.iitgn.ac.in/handle/123456789/3388
dc.description.abstract Intra-cellular tau protein tangles and extra-cellular ?-amyloid plaques are hallmarks of Alzheimer's disease (AD), characterized by the conversion of natively unfolded monomeric protein/peptide into misfolded ?-sheet rich aggregates. Therefore, inhibiting the aggregation cascade or disassembling the pre-formed aggregates becomes a pivotal event in disease treatment. In the present study, we show that Naphthoquinone-Tryptophan hybrids, i.e., NQTrp and Cl-NQTrp significantly disrupted the pre-formed fibrillar aggregates of Tau-derived PHF6 (VQIVYK) peptide and full-length tau protein in vitro, in a dose-dependent manner as evident from ThS assay, CD spectroscopy, and TEM. Molecular dynamics simulation of PHF6 oligomers and fibrils with the Naphthoquinone-Tryptophan hybrids provides a possible structure-function based mechanism-of-action, highlighting the role of hydrophobic interaction and hydrogen bond formation during fibril disassembly. These findings signify the effectiveness of NQTrp and Cl-NQTrp in disassembling fibrillar aggregates and may help in designing novel hybrid molecules for AD treatment.
dc.description.statementofresponsibility by V. Guru KrishnaKumar, Ashim Paul, Ehud Gazit & Daniel Segal
dc.format.extent vol. 8, no. 1
dc.language.iso en en_US
dc.publisher Nature Publishing Group en_US
dc.title Mechanistic insights into remodeled Tau-derived PHF6 peptide fibrils by Naphthoquinone-Tryptophan hybrids en_US
dc.type Article en_US
dc.relation.journal Scientific Reports


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