The role of oxidative stress on tau protein homeostasis in neurodegenerative diseases

Robinson, Anne SkajaTauopathies are a class of neurodegenerative diseases consisting of the aggregation of the aberrant protein tau into paired helical filaments (PHF), which form neurofibrillary tangles (NFT), in the central nervous system. Tauopathies include Pick’s disease, dementia pugilistica, frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17), and Alzheimer’s disease (AD). Recent studies show that the number of NFT directly correlates with the degree of dementia seen in AD [1]. In vivo phosphorylation of the tau protein is a hallmark of many neurodegenerative disorders including Alzheimer’s disease (AD). Recent evidence has also demonstrated the cellular response to oxidative stress may play a role in tau pathogenesis. Here, two model systems were used to determine if a direct mechanistic link could be demonstrated between tau phosphorylation and the oxidative stress pathway. The first model system used was SH-SY5Y cells, a neuronal cultured cell line that endogenously expresses tau. In the second model system, wild-type tau and multiple tau variants were expressed in HEK cells. Cells were treated with hydrogen peroxide to induce the oxidative stress pathway, and changes in tau phosphorylation, tau kinases, and tau chaperones were monitored via western blot. Taken together, the results from these model systems suggest that a direct mechanistic link may exist between tau phosphorylation and the oxidative stress pathway.University of Delaware, Department of Chemical EngineeringM.Ch.E