Discipline: Biological Sciences
Subcategory: Genetics
Session: 1
Room: Exhibit Hall A
Tiara B White - Delaware State University
Co-Author(s): Ashley Anderson, and Michael A. Gitcho
TDP-43 is the major pathological protein in motor neuron disease and frontotemporal dementia and present in ~50% of those with Alzheimer’s disease. TDP-43 functions as a heterogeneous nuclear ribonucleoprotein. TDP-43 has been shown to self-regulate expression by binding to its own mRNA and inhibits translation in order to maintain homeostasis. We hypothesize that the ability of TDP-43 to self-regulate diminishes as pathology accumulates in the cytoplasm to form abnormal inclusion bodies in limbic-predominant age-related TDP-43 encephalopathy (LATE) and AD. Therefore, endogenous TDP-43 may increase expression in the nucleus as pathology forms in the cytosol reducing calcineurin, which increases phosphorylation of TDP-43. To investigate this we will utilize both primary neuronal and cell culture to understand the dynamics associated with TDP-43 and DARPP-32 phosphorylation. Our published research and preliminary data suggest that modulating TDP-43 expression could provide a target for therapeutic intervention and slow the progression of limbic-predominant age-related TDP-43 encephalopathy
Funder Acknowledgement(s): This work was funded by the Alzheimer's Association New Investigator Research Grant: NIRG-12-241456, the National Institute on Aging: 1K01AG042500, Delaware IDeA Network of Biomedical Research Excellence (INBRE) Pilot Award: NIH-NIGMS: 5P20GM103446, NIH-NIGMS Centers of Biomedical Research Excellence (COBRE): 5P20GM103653; and Delaware Economic Development Office Grant from the State of Delaware.
Faculty Advisor: Micheal Gitcho, mgitcho@desu.edu
Role: In this project, I did a cell culture model, protein immunoblot, and BCA assay. I also carried out transfection protocols and statistical analysis.