MAPT and neurodegenerative disease: Furthermore, tau-challenged neuronal models have naturally elicited these oxidative stress responses (Chew et al., 2015), and further pharmacological upregulation of either Nrf2/SKN-1 or FoxO/DAF-16 has ameliorated tau-mediated neurodegenerative disease phenotypes (Chen et al., 2015; Johnson and Johnson, 2015).