JNK signalling regulates antioxidant responses in neurons
Chris Ugbode,
Nathan Garnham,
Laura Fort-Aznar,
Gareth J.O. Evans,
Sangeeta Chawla,
Sean T. Sweeney
Affiliations
Chris Ugbode
Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK
Nathan Garnham
Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK
Laura Fort-Aznar
Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK
Gareth J.O. Evans
Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK
Sangeeta Chawla
Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK; Corresponding author. Department of Biology, University of York, York, YO10 5DD, UK.
Sean T. Sweeney
Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK; Corresponding author. Department of Biology, University of York, York, YO10 5DD, UK.
Reactive oxygen species (ROS) are generated during physiological bouts of synaptic activity and as a consequence of pathological conditions in the central nervous system. How neurons respond to and distinguish between ROS in these different contexts is currently unknown. In Drosophila mutants with enhanced JNK activity, lower levels of ROS are observed and these animals are resistant to both changes in ROS and changes in synapse morphology induced by oxidative stress. In wild type flies, disrupting JNK-AP-1 signalling perturbs redox homeostasis suggesting JNK activity positively regulates neuronal antioxidant defense. We validated this hypothesis in mammalian neurons, finding that JNK activity regulates the expression of the antioxidant gene Srxn-1, in a c-Jun dependent manner. We describe a conserved ‘adaptive’ role for neuronal JNK in the maintenance of redox homeostasis that is relevant to several neurodegenerative diseases.
