Presenter(s)

Prajakta D. Deshpande, Emily M. Snider

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Description

Alzheimer's Disease (AD) is a progressive form of dementia that presents itself in individuals aged 65 years or older. AD is characterized by a decline in memory and cognitive function. Currently, there is no cure for AD though symptomatic treatments are available. One of the hallmarks of AD is the accumulation of β-amyloid plaques formed in the brain due to improper cleavage of the amyloid precursor protein. The extracellular accumulation of β-amyloid plaques triggers the hyperphosphorylation of tau, a microtubule-associated protein that helps stabilize microtubule structures in neurons. In its hyperphosphorylated form, tau loses affinity to bind to the microtubules and can oligomerize. This results in the formation of tau tangles and the destabilization of axons and dendrites (necessary for cellular communication). We employed the GAL4-UAS system in the model organism Drosophila melanogaster to misexpress human Aβ42 within the developing fly retina. Using forward genetic screening, we found N-acetyltransferase 9 (NAT 9) as one of the modifiers for the Aβ42 phenotype. NAT 9 is an enzyme that acetylates microtubules and supports the regulation of microtubule stability. This study aims to understand the role of NAT 9 in Aβ42-mediated neurodegeneration. The overexpression of NAT 9 in GMR>Aβ42 background suppresses the Aβ42-mediated neurodegeneration whereas loss of function of NAT 9 in GMR>Aβ42 results in depigmentation, necrotic spots, and a reduction in eye size as compared to GMR>Aβ42 eye. Our hypothesis is Nat9 may play a role in Aβ42-mediated neurodegeneration.

Publication Date

4-22-2021

Project Designation

Honors Thesis

Primary Advisor

Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium project, College of Arts and Sciences

United Nations Sustainable Development Goals

Good Health and Well-Being

Drosophila Eye Model to Study the Role of NAT 9 in Alzheimer’s Disease-Related Dementia (ADRD)

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