TauLUM, an in vivo Drosophila sensor of tau multimerization, identifies neuroprotective interventions in tauopathy
Year: 2022
Type: article
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.
Source: Cell Reports Methods
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: South Texas Medical Scientist Training Program (STX-MSTP), G330731456, G5551878694, G571033708, G6099097669, Cell Type and Regional Vulnerability in Frontotemporal Dementia, G6527784256, NRSA Training Core (TL1), Training Grant on the Biology of Aging, G9000089312, Bloomington Drosophila Stock Center at Indiana University, Integrated Graduate Training Program in Neuroscience, UTHSCSA
OpenAlex ID: W4295136809