RT Journal Article
SR Electronic
T1 JNK signalling regulates antioxidant responses in neurons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.05.136622
DO 10.1101/2020.06.05.136622
A1 Ugbode, Chris
A1 Garnham, Nathan
A1 Fort-Aznar, Laura
A1 Evans, Gareth
A1 Chawla, Sangeeta
A1 Sweeney, Sean T.
YR 2020
UL http://biorxiv.org/content/early/2020/06/18/2020.06.05.136622.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.