TauLUM, an in vivo Drosophila sensor of tau multimerization, identifies neuroprotective interventions in tauopathy

Simon A. Levy, Gabrielle Zuniga, Elias M. Gonzalez, David Butler, Sally Temple, Bess Frost

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Tau protein aggregates are a defining neuropathological feature of “tauopathies,” a group of neurodegenerative disorders that include Alzheimer's disease. In the current study, we develop a Drosophila split-luciferase-based sensor of tau-tau interaction. This model, which we term “tauLUM,” allows investigators to quantify tau multimerization at individual time points or longitudinally in adult, living animals housed in a 96-well plate. TauLUM causes cell death in the adult Drosophila brain and responds to both pharmacological and genetic interventions. We find that transgenic expression of an anti-tau intrabody or pharmacological inhibition of HSP90 reduces tau multimerization and cell death in tauLUM flies, establishing the suitability of this system for future drug and genetic modifier screening. Overall, our studies position tauLUM as a powerful in vivo discovery platform that leverages the advantages of the Drosophila model organism to better understand tau multimerization.

Original languageEnglish (US)
Article number100292
JournalCell Reports Methods
Volume2
Issue number9
DOIs
StatePublished - Sep 19 2022

Keywords

  • Alzheimer's disease
  • Drosophila
  • neurodegeneration
  • split-luciferase
  • tau

ASJC Scopus subject areas

  • Genetics
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Biotechnology
  • Computer Science Applications

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