Presenter(s)

Steven Gerard Borchers, Prajakta D Deshpande, Neha Gogia

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Description

Alzheimer’s disease (AD), is a neurodegenerative disease which affects mental functions of the patients. This disorder progresses with age and does not have a cure to-date. One of the reasons for the manifestation of AD is the accumulation of amyloid-beta-42 (Aβ42) proteins. In our study, we have used Drosophila as our model organism (as 75% of the genetic machinery is conserved between flies and humans), and have developed a model where when human Aβ42 is misexpressed in the differentiating eye, it triggers cell death in retinal neurons of the eye. We have identified that Lunasin (a soy-based anti-inflammatory protein), can block Aβ42 mediated cell death and thus wanted to test whether NFkB pathway (anti-inflammatory pathway, lead to translation of apoptotic proteins of jun-N Terminal Kinase, JNK pathway), helps lunasin blocking cell death. In order to test this, we developed transgenic flies which can produce human Aβ42 and Aβ42+Lunasin in Drosophila eye and checked the effect of modulating NFkB pathway in this background. Our hypothesis states that manipulating the levels of Relish (component of the Imd-NFkB pathway), could lead to activity variation in JNK pathway in Aβ42+Lunasin flies. To test our hypothesis, we used GAL4/UAS system genetic technique and misexpressed Relish and RelishRNAi in human Aβ42 and Aβ42+Lunasin background and checked for the resultant phenotypes in (1) larval eye discs and (2) adults. Our data shows that downregulation of Relish interferes with Lunasin’s ability to rescue Aβ42 phenotypes and thus leads to eye suppression phenotypes, which suggests that Imd-NFkB pathway plays a positive role in Lunasin’s ability to mitigate the neuronal cell death cause by the accumulation of Aβ42 plaques. These studies have significant bearing on the use of NFkB members as biomarkers or druggable targets and generate new insights into the mechanism by which Aβ42 mediated neurodegeneration cell death can be blocked in future.

Publication Date

4-24-2019

Project Designation

Honors Thesis

Primary Advisor

Amit Singh

Primary Advisor's Department

Biology

Keywords

Stander Symposium project

Role of Relish/NFkB Apoptosis Pathway in Amyloid-beta 42 mediated neurodegeneration in Alzheimer’s disease

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