984B Poster - 15. Models of human disease
Friday April 08, 2:00 PM - 4:00 PM

Authors:
Emily Snider ¹; Prajakta Deshpande ¹; Amit Singh ^1,2,3,4,5

Affiliations:
1) Department of Biology, University of Dayton, Dayton, OH; 2) Premedical Program, University of Dayton, Dayton, OH; 3) Center for Tissue Regeneration & Engineering (TREND), University of Dayton, Dayton, OH; 4) Integrative Science and Engineering (ISE), University of Dayton, Dayton, OH; 5) Center for Genomic Advocacy (TCGA), Indiana State University, Terre Haute, IN

Keywords:
w. genetic modifiers of disease; w. genetic modifiers of disease

Alzheimer's Disease (AD), an age-related progressive form of dementia, is characterized by a decline in cognitive function. Accumulation of the peptide amyloid beta (Aβ42) plaque is one of the characteristics of the disease. 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 the 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. The 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 GMR>Aβ42 background enhances Aβ42-mediated neurodegeneration. The eye antennal imaginal discs of loss-of-function of NAT9 in GMR>Aβ42 background shows the activation of JNK pathway by increased pJNK levels. Hence, here we propose that NAT9 downregulates JNK signaling pathway which can ameliorate Aβ42-mediated neurodegeneration.