Arizona State University, Tempe, AZ
Previous research has suggested a strong correlation between Alzheimer's Disease (AD) and malfunction of the Nuclear Pore Complex (NPC). This brings into question the maintenance of other functions and processes that rely on the regulatory factors of the Nuclear Pore Complex in AD afflicted cells. Research was conducted to analyze the relevance of nuclear transport proteins and regulators in AD and how they may affect the functionality of neural tissue, specifically the proteins IPO4, CAMK4, and NTF2. Analysis of gene expression data for these proteins has suggested that there is a significant level of down regulation in these genes in AD afflicted cells compared to Non-diseased tissue. A comprehensive study was conducted to explore the localization of these proteins in neural cells and to quantify the amount of protein using immunohistochemistry and Western Blot. Mislocalization and variation in protein levels could be indicative of transport errors related to cargo. Lower levels of immunoreactivity for NTF2, an active transport regulator of RAN, suggests there is a correlation between the development of Alzheimer’s and dysfunction in cell transport. Results establish greater importance and need for studies investigating NPC transporters and regulators to gain a holistic understanding of AD at a cellular level. Future plans for study are focused on immunoprecipitation and nuclear cytoplasmic prep to verify binding and localization of proteins. Functional validation of proteins could be conducted through knockouts in cell culture or analysis of the interactions of these proteins with their cargo or tau.