Cl-NQTrp Alleviates Tauopathy Symptoms in a Model Organism through the Inhibition of Tau Aggregation-Engendered Toxicity

Moran Frenkel-Pinter, Sharon Tal, Roni Scherzer-Attali, Malak Abu-Hussien, Idan Alyagor, Tal Eisenbaum, Ehud Gazit, Daniel Segal

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Alzheimer's disease (AD) is the most abundant tauopathy and is characterized by Aβ-derived plaques and tau-derived tangles, resulting from the unfolding of the corresponding monomeric subunits into ordered β-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 Drosophila 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 Aβ and tau.

Original languageAmerican English
Pages (from-to)73-82
Number of pages10
JournalNeurodegenerative Diseases
Issue number2-3
StatePublished - 1 Feb 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 S. Karger AG, Basel.


  • Alzheimer?s disease
  • Cl-NQTrp
  • Drosophila melanogaster
  • PHF6
  • Protein aggregation
  • Protein misfolding
  • Tau protein


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