National Conference on Undergraduate Research (NCUR)/Poster Presentation/ April 12, 2021
Abstract: Misregulation of Tip60 in the Tau Drosophila Alzheimer’s Disease Model
Neurofibrillary tangles, which block axonal transport of neurons due to hyperphosphorylation of the Tau protein, are a common feature of Alzheimer’s Disease (AD). We have previously shown that Tip60 histone acetyltransferase (HAT)/histone deacetylase 2 (HDAC2) mediated histone acetylation is critical in regulating neural gene expression and that this balance goes awry in the AD-associated amyloid precursor protein (APP) Drosophila model. We have identified a set of synaptic plasticity genes that are Tip60/HDAC2 gene targets and have shown that they are disrupted in the AD fly brain. The goal of this project is to assess whether these genes functionally contribute to AD associated neurodegeneration via the Tau AD pathway. This project was conducted in two parts. First, we performed a behavioral analysis using wildtype Drosophila larvae and Drosophila larvae expressing Tau in the nervous system. Behavioral assays, including learning and memory, gustatory, and olfactory, were conducted to test the cognitive defects of the Tau model. Our results show that the Tau model has decreased cognitive abilities in comparison to the wild type. We next used real-time PCR to assess the expression levels of Tip60 and its target genes. Our results revealed that these genes were misregulated in the Tau flies, suggesting that the cognitive defects we observe are at least in part, due to the misregulation of Tip60 and its target genes. Our results reaffirm the importance of Tip60 HAT/HDAC2 homeostasis in AD and reveal the potential of improving cognitive function through restoring this epigenetic balance.
Abstract: Misregulation of Tip60 in the Tau Drosophila Alzheimer’s Disease Model
Neurofibrillary tangles, which block axonal transport of neurons due to hyperphosphorylation of the Tau protein, are a common feature of Alzheimer’s Disease (AD). We have previously shown that Tip60 histone acetyltransferase (HAT)/histone deacetylase 2 (HDAC2) mediated histone acetylation is critical in regulating neural gene expression and that this balance goes awry in the AD-associated amyloid precursor protein (APP) Drosophila model. We have identified a set of synaptic plasticity genes that are Tip60/HDAC2 gene targets and have shown that they are disrupted in the AD fly brain. The goal of this project is to assess whether these genes functionally contribute to AD associated neurodegeneration via the Tau AD pathway. This project was conducted in two parts. First, we performed a behavioral analysis using wildtype Drosophila larvae and Drosophila larvae expressing Tau in the nervous system. Behavioral assays, including learning and memory, gustatory, and olfactory, were conducted to test the cognitive defects of the Tau model. Our results show that the Tau model has decreased cognitive abilities in comparison to the wild type. We next used real-time PCR to assess the expression levels of Tip60 and its target genes. Our results revealed that these genes were misregulated in the Tau flies, suggesting that the cognitive defects we observe are at least in part, due to the misregulation of Tip60 and its target genes. Our results reaffirm the importance of Tip60 HAT/HDAC2 homeostasis in AD and reveal the potential of improving cognitive function through restoring this epigenetic balance.