Honors Theses
Advisor
Amit Singh
Department
Biology
Publication Date
12-2021
Document Type
Honors Thesis
Abstract
Alzheimer's Disease (AD), an age-related progressive form of dementia, is characterized by a decline in cognitive function. One of the hallmarks of AD is extracellular accumulation of β-amyloid plaques (Aβ42) in the brain. The accumulation of these Aβ42 plaques trigger the hyperphosphorylation of tau, a microtubule associated protein, thereby destabilizing the microtubules. This results in the intracellular accumulation of neurofibrillary tangles. We employed the Gal4/UAS system in Drosophila melanogaster to misexpress human Aβ42 within the developing fly retina, exhibiting AD-like neuropathology. Accumulation of Aβ42 plaque(s) triggers aberrant activation of signaling pathways like the JNK pathway resulting in neuronal cell death by unknown mechanism(s). Using forward genetic screening, we identified N-acetyltransferase 9 (NAT9) as one of the genetic modifiers of GMR>Aβ42 reduced eye phenotype. A previous study suggests that NAT9 stabilizes microtubules by acetylation of tubulins, thereby inhibiting JNK signaling. This study aims to understand the role of NAT9 in Aβ42-mediated neurodegeneration. The gain-of-function of NAT9 in GMR>Aβ42 background suppresses the Aβ42-mediated neurodegeneration. Whereas loss-of-function of NAT9 in the background of GMR>Aβ42 results in depigmentation, necrotic spots, and a reduction in eye size as compared to GMR>Aβ42 fly eye phenotype. The eye discs of knockdown of NAT9 shows the activation of JNK pathway by increased pJNK levels. This worsened eye phenotype is rescued when JNK pathway was downregulated. Hence, here we propose that NAT9 downregulates JNK signaling pathway which in turn could ameliorate Aβ42-mediated neurodegeneration.
Permission Statement
This item is protected by copyright law (Title 17, U.S. Code) and may only be used for noncommercial, educational, and scholarly purposes.
Keywords
Undergraduate research
eCommons Citation
Snider, Emily E., "Investigating the Role of Microtubule Binding Protein, NAT9, in the Drosophila Eye Model of Alzheimer’s Disease" (2021). Honors Theses. 341.
https://ecommons.udayton.edu/uhp_theses/341
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