Presentation description

Neurodegenerative diseases such as Alzheimer's are marked by the toxic buildup of Tau, a protein that normally stabilizes neurons but becomes harmful when abnormally folded. Recent research in human cell models suggests that a gene called ANKLE2 may protect against Tau aggregation, but its function in adult neurons remains unclear. Preliminary studies by our lab have shown that ANKLE2 knockdown intensifies human Tau-induced eye defects when expressed in developing Drosophila, leading us to investigate its role in adult neurons.
In this study, I use Drosophila melanogaster (fruit flies) a genetically tractable model that shares over 75% of disease-related genes with humans, to examine the impact of ANKLE2 loss on Tau induced neurodegeneration in adult neurons. Using the UAS-GAL4 system with temperature sensitive controls, I specifically knock down ANKLE2 in adult neurons and measure neurodegeneration by tracking lifespan, motor performance, and neuronal cell death over time.
Early findings show that ANKLE2 deficiency in adult neurons worsens Tau-associated phenotypes, resulting in reduced lifespan, impaired climbing and flight ability, and increased neuronal loss. These results suggest that ANKLE2 plays a protective role against Tau toxicity in adult neurons. Understanding this relationship will help clarify the genetic factors that influence Tau pathology and may guide future research into targeted therapies for Alzheimer's disease and related tauopathies.