Role of calcium signaling in Aβ42-mediated neurodegeneration in a Drosophila model of Alzheimer’s disease
Dena M. Schaeffer, Catherine Jean Yeates
Alzheimer’s disease (AD) is a neurodegenerative disease that affects more than five million individuals in the United States and is the sixth leading cause of death. While there is currently no cure for the disease, it is a highly investigated topic of research. Aberrant calcium signaling has also been implicated in cancer and other neurological diseases besides AD. The Drosophila melanogaster eye model is an excellent system to study AD due to the highly conserved genetic machinery shared between flies and humans. A transgenic fly model of AD was generated, where the GAL4/UAS system was developed to ectopically express high levels of human Aβ42 peptides in the differentiating photoreceptor neurons in the fly eye. This system is used to determine whether modulating the function of the calcium signaling pathway can modify Aβ42-mediated neurodegeneration. We used RNAi to knock down six components of the calcium signaling pathway (StimRNAi, SERCARNAi, ORAIRNAi, Inx2RNAi, IP3RRNAi, and Plc 21CRNAi) in an Aβ42 background in the eye and observed the effects in both eye antennal imaginal discs and adult eyes. Similarly, we overexpressed four UAS components of the calcium signaling pathway (Stim, ORAI, SERCA, IP3R). Our results showed evidence that knocking down these components of the pathway may ameliorate the neurodegeneration mediated by Aβ42. Likewise, overexpressing the components furthered our evidence that the calcium signaling pathway has a role in AD. Our research further implicates intracellular calcium signaling in neurodegenerative disorders. Further research will determine the molecular mechanisms linking calcium signaling with Aβ42-mediated neurodegeneration.
Primary Advisor's Department
Stander Symposium project, College of Arts and Sciences
United Nations Sustainable Development Goals
Good Health and Well-Being
"Role of calcium signaling in Aβ42-mediated neurodegeneration in a Drosophila model of Alzheimer’s disease" (2020). Stander Symposium Projects. 1984.