Characterization of Tau Phosphorylation During the Differentiation of Human Embryonic Stem Cells

Abstract

Alzheimer's disease is the seventh leading cause of death in the United States with an estimated cost of 100 billion dollars. The severity of this neurodegenerative disease is strongly correlated with the number of neurofibrilary tangles (NFT) composed of hyperphosphorylated tau, a microtubule associated protein. The phosphorylation of tau is known to be tightly regulated by glycogen synthase kinase 3Beta (GSK-3Beta) and cyclin-dependent kinase 5 (Cdk-5). These two kinases also play a vital role in neuronal cell development. We characterized the phosphorylation of tau and expression of tau, GSK-3Beta, and Cdk-5 during early embryo development using human embryonic stem cells (hESC) as our model system. We determined that GSK-3Beta plays an important role in the regulation of proliferation, tau phosphorylation, and neuroectodermal differentiation of hESC. However, the inhibition of Cdk-5 did not significantly change hESC proliferation and the expression of tau, GSK-3Beta, and Cdk-5 throughout hESC differentiation.