Oxidative stress is a central pathomechanism in Alzheimer's disease (AD) and other diseases with tau pathology. The Nrf2 transcription factor induces detoxification enzymes and improves tau pathology and cognition. Its homologue in C. elegans is SKN-1. We previously showed that the worm tau homologue, PTL-1, regulates neuronal aging and lifespan. Here, we tested PTL-1's involvement in the stress response. ptl-1 mutant animals are hypersensitive to oxidative stress and are defective in stress-mediated nuclear accumulation of SKN-1. This defect can be rescued by PTL-1 re-expression under the control of the ptl-1 promoter. Given the close relationship between aging and stress tolerance, we tested lifespan and found that PTL-1 and SKN-1 regulate longevity via similar processes. Our data also suggest that PTL-1 functions via neurons to modulate SKN-1, clarifying the role of this protein in the stress response and longevity.
Keywords: C. elegans; PTL-1; SKN-1; lifespan; neurons; oxidative stress.
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.