College of Arts & Sciences

Sundus Pervez

College of Arts & Sciences

Biological Sciences

Faculty Mentor: Dr. Felice Elefant Biology

Haolin Zhang Co-Mentor

Generation and Characterization of Aβ;Tip60 fly line

Histone acetylation modifications play a crucial role in Alzheimer’s disease (AD) pathogenesis. The appropriate levels of histone acetyltransferases (HATs) and histone acetylation homeostasis are disrupted in AD. Pilot studies in our lab provide solid evidence of neuroprotective function of Tip60 HAT against amyloid precursor protein (APP) induced AD pathology. Restoring Tip60 levels in APP overexpressed fly brain relieves epigenetic transcriptional repression, reduces neuronal apoptosis and revives cognition. Here we develop a double transgenic fly model (Aβ42;Tip60) that allows us to restore Tip60 level in Aβ42. To validate Tip60 gene expression in Aβ42;Tip60 flies, qPCR and Western blot are performed. Both Tip60 mRNA and protein levels are restored in the Aβ42;Tip60 fly line. Tip60 overexpression can sustainably suppress histone deacetylases 1/2 (HDAC1/2) expression and maintain appropriate histone acetylation levels over time, implying restored epigenetic homeostasis. We will monitor whether Aβ-induced AD pathologies can be rescued by Tip60 action. We discuss the possibility that Tip60 may play essential neuroprotective role in Aβ-induced AD neurodegeneration.