Drosophila notal bristle as a novel assessment tool for pathogenic study of Tau toxicity and screening of therapeutic compounds

Po An Yeh, Ju Yi Chien, Chih Chung Chou, Yu Fen Huang, Chiou Yang Tang, Hsiang Yu Wang, Ming-Tsan Su*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

16 引文 斯高帕斯(Scopus)

摘要

To elucidate the Tau gain-of-toxicity functional mechanism and to search for potential treatments, we overexpressed human Tau variants (hTau) in the dorsal mesothorax (notum) of Drosophila. Overexpression of Tau variants caused loss of notal bristles, and the phenotype was used for evaluating toxicity of ectopic Tau. The bristle loss phenotype was found to be highly associated with the toxicity of hyperphosphoryled Tau in flies. We have shown that the bristle loss phenotype can be rescued either by reducing Glycogen synthase kinase 3β (GSK3β)/Shaggy (Sgg) activity or overexpressing Bβ2 regulatory subunits of PP2A. Elevated expression of the Drosophila Bβ2 homolog, Twins (Tws), also alleviated neuritic dystrophy of the dorsal arborization (da) neuron caused by Tau aggregation. Additionally, lowering endogenous Tau dosage was beneficial as it ameliorated the bristle loss phenotype. Finally, the bristle loss phenotype was used to evaluate the efficacy of potential therapeutic compounds. The GSK3β inhibitor, alsterpaullone, was found to suppress toxicity of Tau in a concentration-dependent manner. The notum of Drosophila, thus, provides a new tool and insights into Tau-induced toxicity. It could also potentially assist in screening new drugs for possible therapeutic intervention.

原文英語
頁(從 - 到)510-516
頁數7
期刊Biochemical and Biophysical Research Communications
391
發行號1
DOIs
出版狀態已發佈 - 2010 一月 1

ASJC Scopus subject areas

  • 生物物理學
  • 生物化學
  • 分子生物學
  • 細胞生物學

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