Sexually Dimorphic Heat Shock Protein Induction in a Drosophila melanogaster Model of Glial Tauopathy



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Tauopathies are a broad class of neurodegenerative diseases characterized by aggregates of the microtubule-associated protein tau in both neurons and glia. Many tauopathies exhibit sexual dimorphism in their onset, progression, and severity. We have used a D. melanogaster model of glial tauopathy to dissect the effect of both tau pathology and sex on heat shock protein (HSP) induction. HSPs are molecular chaperones recruited in response to stress that are perplexingly unable to regulate tau proteotoxicity in tauopathies. In our studies, ten-day-old glial tau transgenic and control flies were exposed to heat shock (HS), and we found that the additive stress of tau and HS resulted in selective upregulation of Hsp27 and Hsp70 and suppression of Hsp23 in males. Remarkably, a more pronounced, global HS response was observed in females, as Hsp22, Hsp27, Hsp60, Hsc70, Hsp70, and Hsp83 were all upregulated. Moreover, basal Hsp27 and Hsp83 were suppressed in the presence of glial tau in females only. HSF1, a transcriptional regulator of HSPs, was induced by tau in males but female HSF1 was only induced with the compounded stress of both tau and HS. These robust results warrant further investigation into mechanisms of the chaperone-mediated stress response towards tau and sex-specific vulnerabilities.



Neurodegeneration, Heat Shock Protein, Sexual Dimorphism, Tauopathy, Drosophila