Role of Relish/NFkB Apoptosis Pathway in Amyloid-beta 42 Mediated Neurodegeneration in Alzheimer’s Disease
Steven G Borchers, Neil William Glenn, Neha Gogia
Alzheimer’s disease (hereafter AD) is a progressive neurodegenerative disorder which affects the cognitive functions of the patients. This disease does not have a cure at this point. One of the reasons for the manifestation of AD is the accumulation of amyloid-beta-42 (Aβ42) plaques. Several animal models have been developed to study AD. We have developed a Drosophila eye model where human Aβ42 is misexpressed in the differentiating eye, which triggers neuronal death in the retinal neurons of the eye. Our lab has identified that a soy based protein, Lunasin, can be employed to block Aβ42 mediated cell death. Lunasin is known to block inflammation through downregulating the NFkB pathway. This pathway leads to the translation of apoptotic proteins included in the jun-N Terminal Kinase (JNK) pathway. We have developed transgenic flies which can produce both (human Aβ42 and soy protein Lunasin) in the Drosophila eye protein. These flies have normal eyes as Lunasin blocks Aβ42 mediated neurodegeneration. I want to test how Lunasin prevents neuronal death observed in our Aβ42 accumulation model in Drosophila eye. I propose to genetically change the activity of NFKB pathway kinases Relish and Cactus in transgenic flies where we have introduced human Aβ42 and Lunasin. I have generated transgenic and mutant flies which can be used for gain- of-function as well loss-of-function of these pathway members to observe their effect on Aβ42 neurodegenerative phenotype. I will observe these interactions at three developmental time points of larval eye imaginal disc, pupal retina and the adult eye. By the end of the twelve-week program, I expect to have significant amount of data to address this hypothesis and generate new insight into the mechanism by which Aβ42 mediated neurodegeneration occurs in AD. These studies will have significant bearing on use of NFKB members as biomarkers or druggable targets for AD in future.
Honors Thesis - Graduate
Primary Advisor's Department
Stander Symposium poster
"Role of Relish/NFkB Apoptosis Pathway in Amyloid-beta 42 Mediated Neurodegeneration in
Alzheimer’s Disease" (2017). Stander Symposium Posters. 878.