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Karger AG","issue":"2-3","license":[{"start":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T00:00:00Z","timestamp":1476921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,10,20]],"date-time":"2016-10-20T00:00:00Z","timestamp":1476921600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurodegener Dis"],"published-print":{"date-parts":[[2017]]},"abstract":"<jats:p>Alzheimer's disease (AD) is the most abundant tauopathy and is characterized by A\u03b2-derived plaques and tau-derived tangles, resulting from the unfolding of the corresponding monomeric subunits into ordered \u03b2-sheet oligomers and fibrils. Intervening in the toxic aggregation process is a promising therapeutic approach, but, to date, a disease-modifying therapy is neither available for AD nor for other tauopathies. Along these lines, we have previously demonstrated that a small naphthoquinone-tryptophan hybrid, termed NQTrp, is an effective modulator of tauopathy in vitro and in vivo. However, NQTrp is difficult to synthesize and is not very stable. Therefore, we tested whether a more stable and easier-to-synthesize modified version of NQTrp, containing a Cl ion, namely Cl-NQTrp, is also an effective inhibitor of tau aggregation in vitro and in vivo. Cl-NQTrp was previously shown to efficiently inhibit the aggregation of various amyloidogenic proteins and peptides. We demonstrate that Cl-NQTrp inhibits the in vitro assembly of PHF6, the aggregation-prone fragment of tau, and alleviates tauopathy symptoms in a transgenic &lt;i&gt;Drosophila&lt;\/i&gt; model through the inhibition of tau aggregation-engendered toxicity. These results suggest that Cl-NQTrp could be a unique potential therapeutic for AD since it targets aggregation of both A\u03b2 and tau.<\/jats:p>","DOI":"10.1159\/000448518","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T21:02:48Z","timestamp":1476910968000},"page":"73-82","source":"Crossref","is-referenced-by-count":22,"title":["Cl-NQTrp Alleviates Tauopathy Symptoms in a Model Organism through the Inhibition of Tau Aggregation-Engendered 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