Tau-Induced Suppression of Chaperone Stress Response in a Drosophila Model of Glial Tauopathy

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dc.contributorWoodard, Craig
dc.contributorMcMenimen, Kathryn
dc.contributor.advisorColodner, Kenneth
dc.contributor.authorKahlson, Martha
dc.date.accessioned2015-06-30T13:02:41Z
dc.date.available2015-06-30T13:02:41Z
dc.date.gradyear2015en_US
dc.date.issued2015-06-30
dc.descriptionRecipient of the Ruth Estelle Mills Zencey Award for excellence in scientific writing.en_US
dc.description.abstractFilamentous inclusions of the protein tau in neuronal and glial cells characterize neurodegenerative tauopathies, such as Alzheimer’s disease (AD). The presence of these tau aggregates implies a dysfunction in the chaperone system, the cellular machinery responsible for preventing abnormal accumulation of misfolded proteins. One family of chaperone proteins, heat-shock proteins (HSPs), are synthesized at higher levels in response to cellular stress, and are capable of preventing and repairing protein damage. A promising therapeutic target, these HSPs are among the most potent suppressors of neurodegeneration in animal models, as their upregulation has been shown to prevent and even reverse disease pathology. Why then are endogenous chaperones unable to prevent the protein malfunction and aggregation that characterizes these disorders? Evidence suggests that an age-dependent decline and/or disease-related dysfunction in the protein quality control system may be to blame. In order to better understand heat-shock protein expression in aging and in neurodegenerative disease, a time-course of HSP expression at the mRNA level over the lifespan of the fly was investigated in a Drosophila melanogaster model of glial tauopathy and in control flies lacking the tau transgene. Control flies exposed to chronic thermal stress showed an age-dependent attenuation of HSP expression, supporting past evidence of age-related decline in the protein quality control system. Additionally, we observed dramatic, targeted suppression of the chaperone stress response in flies expressing tau in glial cells, suggesting a possible mechanism of tau-induced toxicity in AD and other tauopathies.en_US
dc.description.sponsorshipNeuroscience and Behavioren_US
dc.identifier.urihttp://hdl.handle.net/10166/3668
dc.language.isoen_USen_US
dc.rights.restrictedrestricteden_US
dc.subjecttauen_US
dc.subjecttauopathyen_US
dc.subjectAlzheimer's diseaseen_US
dc.subjectchaperone systemen_US
dc.subjectHSPen_US
dc.subjectgliaen_US
dc.subjectneurodegenerative diseaseen_US
dc.subjectDrosophilaen_US
dc.titleTau-Induced Suppression of Chaperone Stress Response in a Drosophila Model of Glial Tauopathyen_US
dc.typeThesis
mhc.degreeUndergraduateen_US
mhc.institutionMount Holyoke College

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