Hexachlorophene reduces Tau aggregation and potential therapeutic agent for treatment of Alzheimer’s disease
Poster Feb 13, 2017
Vetriselvan Manavalan, Andrew Rosenblum, Mayank Kesarwani and Umesh Jinwal
Alzheimer’s disease (AD) is a rapidly progressive neurodegenerative disease that affects over 5 million people in the United States alone. The molecular mechanism of AD pathogenesis is not completely understood yet and there only exist very few pharmacological means of intervention for the disease. Tau, a microtubule-associated protein, plays a vital role in stabilizing microtubule networks in neurons. An increase in phosphorylation of tau (hyper phosphorylation) leads to aggregation of the protein resulting in neurofibrillary tangles, a pathological hallmark associated with Alzheimer’s disease (AD). The identification of pharmacological agents that can help decrease levels of phosphorylated tau would be advantageous. Recent work in our laboratory has found that the molecule hexachlorophene can regulate levels of tau in cellular models. Our validation experiments using hexachlorophene showed significant reduction of both total and phosphorylated forms of endogenous tau in M17 neuroblastoma cells, inducible tau in HEK280 cells and over-expressed tau in HeLa C3 cells. We also analyzed effect of hexachlorophene on various pathological forms of tau such as the phosphoserine 396 tau form that localizes to the soluble fraction. Treatment with hexachlorophene decreased levels of phospho serine 396 tau in soluble fraction. Additionally, staining with Thioflavin-S clearly indicates a potential reduction in tau aggregation upon hexachlorophene treatment. Overall, our data suggest that hexachlorophene could be a potential drug molecule for the treatment of tau proteinopathies and AD.
Primary Human Hepatocyte (PHH) culture provides the closest in vitro model to human liver that can produce a metabolic profile of a given drug very similar to that found in vivo. Recently we have developed an easy-to-assemble user-friendly in vitro Primary Human Hepatocyte (PHH) 3D-spheroid modelREAD MORE