CHIP Expression Based on Age and Sex in a Drosophila melanogaster Model of Glial Tauopathy

Abstract

Protein misfolding and aggregation cause harm in the body by contributing to the development of neurodegenerative diseases. Tauopathies are a class of neurodegenerative disorders including Alzheimer’s disease that are characterized by the aggregation of the protein tau. There are several systems in place to prevent the onset of disease and maintain proteostasis in the cell. The ubiquitin proteasome system allows for protein degradation through enzymes that add ubiquitin to misfolded proteins, leading to their degradation by the proteasome. Additionally, heat shock proteins (HSPs) are a family of molecular chaperones that respond to stress and assist in the refolding of misfolded proteins. The C terminal HSP70 binding protein (CHIP) is a co-chaperone of two HSPs and functions as an E3 ligase in the ubiquitin proteasome pathway, targeting HSP substrates including tau for degradation by the proteasome by catalyzing the addition of ubiquitin to the proteins. Despite these systems, tauopathies are able to persist. Multiple factors, including age and sex, play a role in tauopathies. The purpose of this project is to determine how the expression of CHIP is impacted by age and sex in glial tauopathies in Drosophila Melanogaster, gaining insight into the response of CHIP in these diseases. My results highlight sexual dimorphisms in the impact of aging on CHIP expression. I also found that CHIP becomes downregulated in response to heat stress in the presence of glial tau, potentially explaining why tauopathies can persist. Overall, these findings contribute to an increased understanding of the mechanisms behind the development of tauopathies, which could be applied in the future in the development of therapeutics for neurodegenerative disease.