Biophysical and Pathophysiological Studies of TDP-43/Tau Interaction

This study aims to investigate the dynamic relationship between TDP-43 and Tau proteins in normal and pathological contexts. We will characterize the interaction between TDP-43 and Tau by probing their binding using NMR and surface plasmon resonance. We will also test small molecules and peptides for their efficacy in mutilating or disrupting TDP-43/Tau interaction. Additionally, our study aims to determine the physiological and pathological consequences of TDP-43 and Tau interaction by examining phenotypes, behaviors, and cellular interactions using a humanized knock-in disease model in which normal aging and axonal injury will serve as the paradigm for examining lifespan changes that do not involve genetic overexpression or pharmacological initiation. The identification of binding partners and the role played by phosphorylation within the TDP-43/Tau protein-protein network will further expand our understanding of neurodegenerative disease development. The findings from this study will contribute to the development of novel therapeutics approaches targeting the interaction between TDP-43 and Tau spawning generation first-in-class therapeutics for AD and other neurodegenerative diseases.