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Presentation Time: 9:25-9:45
Home University: UNC-Chapel Hill
Research Mentor: Dr. Todd Cohen, Neurology Department
Program: SURF
Research Title: Investigating the Phosphorylation of HDAC6 in Protection Against Alzheimer’s Disease

Alzheimer’s disease (AD) is characterized by the accumulation of waste proteins, often referred to as tangles, which are considered the primary contributor to neuronal death. The main component of these tangles is tau protein which undergoes modifications that correlate with cognitive decline. Of these modifications, lysine acetylation is particularly relevant as it strongly accelerates tangle formation. Histone deacetylase 6 (HDAC6) is known to remove acetyl groups from tau protein, and thus, serves as a potential modifier for AD pathogenesis. Here, we hypothesize that HDAC6 activity is regulated by specific kinases via phosphorylation at Ser-22. In this study, we performed subcellular fractionation, co-immunoprecipitation, and immunofluorescence approaches using HEK-293 cells. We further investigate which kinases most effectively interact with and phosphorylate HDAC6, and analyze the downstream events of HDAC6 phosphorylation, such as nuclear-cytoplasmic shuttling. Our results showed that the Parkinson’s disease (PD)-relevant kinase LRRK2, and GSK-3, a kinase long implicated in AD progression, exhibited potent kinase activities towards HDAC6 and mediated subcellular translocation of HDAC6. This study highlights potential upstream enzymes of HDAC6 and the succeeding events of HDAC6 phosphorylation. Further investigation of these kinases in disease models could reveal alternative strategies for AD treatment and potentially bridge gaps between AD and PD pathologies.