Inhibition of Tau filament formation by conformational modulation

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dc.contributor.author Akoury, Elias
dc.contributor.author Gajdat, Michal
dc.contributor.author Pickhardt, Marcus
dc.date.accessioned 2019-03-22T08:15:56Z
dc.date.available 2019-03-22T08:15:56Z
dc.date.copyright 2013 en_US
dc.date.issued 2019-03-22
dc.identifier.issn 1520-5126 en_US
dc.identifier.uri http://hdl.handle.net/10725/10251
dc.description.abstract Antiaggregation drugs play an important role in therapeutic approaches for Alzheimer’s disease. Although a large number of small molecules that inhibit the aggregation of the tau protein have been identified, little is known about their mode of action. Here, we reveal the mechanism and the nature of tau species that are generated by interaction of tau with the organic compound pthalocyanine tetrasulfonate (PcTS). We demonstrate that PcTS interferes with tau filament formation by targeting the protein into soluble oligomers. A combination of NMR spectroscopy, electron paramagnetic resonance, and small-angle X-ray scattering reveals that the soluble tau oligomers contain a dynamic, noncooperatively stabilized core with a diameter of 30–40 nm that is distinct from the core of tau filaments. Our results suggest that specific modulation of the conformation of tau is a viable strategy for reduction of pathogenic tau deposits. en_US
dc.language.iso en en_US
dc.title Inhibition of Tau filament formation by conformational modulation en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201900590 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Journal of the American Chemical Society en_US
dc.journal.volume 135 en_US
dc.journal.issue 7 en_US
dc.article.pages 2853-2862 en_US
dc.identifier.ctation Akoury, E., Gajda, M., Pickhardt, M., Biernat, J., Soraya, P., Griesinger, C., ... & Zweckstetter, M. (2013). Inhibition of tau filament formation by conformational modulation. Journal of the American Chemical Society, 135(7), 2853-2862. en_US
dc.author.email elias.akoury@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://pubs.acs.org/doi/abs/10.1021/ja312471h en_US
dc.orcid.id https://orcid.org/0000-0001-5202-8935 en_US
dc.author.affiliation Lebanese American University en_US

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