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The CK1 family of protein kinases are overexpressed in AD brains and have been linked with tau phosphorylation. For our study, we will be looking at two CK1 isoforms, CK1δ and CK1ε. Endogenous CK1δ greatly contributes to basal phosphorylation in the sample cells, while an overexpression of both isoforms saw a spike in tau phosphorylation. Previous studies have also shown that CK1δ can phosphorylate at least 15 sites in PHF-tau. We are trying to develop small-molecule kinase inhibitors that can better bind to tau protein than ATP, thereby reducing phosphorylation, maintaining cytoskeletal integrity, and stabilizing cell viability. Our research group has identified a series of compounds that function as ATP-competitive inhibitors of CK1d and CK1e. Docking studies are being performed for these compounds onto the X-ray crystal structure of CK1δ and CK1ε to understand the protein-inhibitor interactions. The results from the docking studies are presented here.
Xavier University of Louisiana
Synthesis, Ck1δ, Ck1ε Inhibitors, Alzheimer's Disease
Huynh, Phong; Sridhar, Jayalakshmi; and Tran, Linh, "Design and Synthesis of Ck1δ and Ck1ε Inhibitors as Therapeutics for Alzheimer's Disease" (2020). Building Infrastructure Leading to Diversity (BUILD). 11.