Drosophila Eye Model to Study the Role of Steroid-Responsive Ecdysone Pathway in Alzheimer\u27s Disease

Alzheimer’s disease, the most common form of dementia, is a chronic neurodegenerative condition that affects nearly 44 million people worldwide. The hallmark of Alzheimer’s pathology is the accumulation of extracellular Aβ-42 protein plaques, which cause inflammation and neuronal death in the brains of affected patients. Currently, no proper early detection methods or cures exist, but promising evidence is arising from studying the development of nervous tissue in model organisms like Drosophila melanogaster. In order to better understand the mechanism by which this disease progresses and its interactions amongst the unique nature of nerve cells, we misexpressed human Aβ-42 in the eye of Drosophila, which forms amongst the differentiating photoreceptor cells. This results in a strong neurodegenerative phenotype, which we strive to rescue through genetic and developmental techniques. This project focuses on two signaling pathways that have important implications in the development of AD. The Hippo pathway is a conserved signaling cascade that that is essential for the proper regulation of organ growth in Drosophila and vertebrates. Previous research has shown that downregulation of this cascade causes an increase in cell proliferation in developing somatic epithelium and nervous tissue, exhibiting neuroprotective effects. Recently, research has shown that the related Ecdysone signaling pathway modulates Hippo transcriptional activity in imaginal disc cells. The Ecdysone coactivator Taiman forms a unique transcriptional complex with the Hippo transcription factor Yorkie, suppressing expression of canonical Hippo targets and inducing transcription of germline stem cell factors in regions that have already differentiated. We have tested two new modulators of the Hippo signaling pathway, a downstream target protein called Ajuba and the related Ecdysone pathway, to study their interactions, ability to induce germline-like growth, and prevent the degradation of eye tissue during development in an AD Drosophila eye model. We will present our progress and future direction.https://ecommons.udayton.edu/stander_posters/1757/thumbnail.jp