Tauopathies are a subclass of neurodegenerative diseases characterized by the aggregation of hyperphosphorylated tau protein in the central nervous system (CNS). Meanwhile, heat shock proteins (HSPs) play an essential role in sustaining proteostasis by supporting protein folding and preventing harmful aggregation. Perplexingly, HSPs are unable to manage tau proteotoxicity. As a result, we seek to uncover how glial tau aggregation and age impact the chaperone response in a Drosophila melanogaster model by performing a holistic screening of HSP induction when faced with these stressors. Through the use of the GAL4/UAS system, we overexpressed the human tau isoform 0N4R in female D. melanogaster glia. Eight experimental groups were then created to test the effects of glial tau, age, and induced heat shock on HSP induction. D. melanogaster mRNA was then extracted from the CNS via TRIzol homogenization, and isopropanol precipitation, and all samples were subjected to qRT-PCR. In female flies, each HSP had a unique heat shock response suggesting the importance of each protein’s unique contribution to the proteostasis machinery. Notably, Hsp70 and Hsp27 demonstrated an increased expression in the presence of tau that disappeared with age, and Hsp26 levels remained constant across all conditions. Basal expression was also analyzed, and a dramatic decrease in Hsp27 basal expression in young flies suggests that this protein plays an intrinsic role in the early stages of tau aggregation and expression. Because tauopathies typically exhibit sexual dimorphism in their onset, progression, and severity, future directions include comparing these results to male samples.

Heat shock protein induction in Drosophila melanogaster as a model system of glial tauopathy

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