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JNK signalling regulates antioxidant responses in neurons

View ORCID ProfileChris Ugbode, Nathan Garnham, Laura Fort-Aznar, Gareth Evans, Sangeeta Chawla, View ORCID ProfileSean T. Sweeney
doi: https://doi.org/10.1101/2020.06.05.136622
Chris Ugbode
1Department of Biology, University of York, York, YO10 5DD, UK
2York Biomedical Research Institute, University of York, York, YO10 5DD, UK
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  • ORCID record for Chris Ugbode
Nathan Garnham
1Department of Biology, University of York, York, YO10 5DD, UK
2York Biomedical Research Institute, University of York, York, YO10 5DD, UK
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Laura Fort-Aznar
1Department of Biology, University of York, York, YO10 5DD, UK
2York Biomedical Research Institute, University of York, York, YO10 5DD, UK
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Gareth Evans
1Department of Biology, University of York, York, YO10 5DD, UK
2York Biomedical Research Institute, University of York, York, YO10 5DD, UK
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Sangeeta Chawla
1Department of Biology, University of York, York, YO10 5DD, UK
2York Biomedical Research Institute, University of York, York, YO10 5DD, UK
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  • For correspondence: sean.sweeney@york.ac.uk sangeeta.chawla@york.ac.uk
Sean T. Sweeney
1Department of Biology, University of York, York, YO10 5DD, UK
2York Biomedical Research Institute, University of York, York, YO10 5DD, UK
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  • ORCID record for Sean T. Sweeney
  • For correspondence: sean.sweeney@york.ac.uk sangeeta.chawla@york.ac.uk
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 18, 2020.
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JNK signalling regulates antioxidant responses in neurons
Chris Ugbode, Nathan Garnham, Laura Fort-Aznar, Gareth Evans, Sangeeta Chawla, Sean T. Sweeney
bioRxiv 2020.06.05.136622; doi: https://doi.org/10.1101/2020.06.05.136622
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JNK signalling regulates antioxidant responses in neurons
Chris Ugbode, Nathan Garnham, Laura Fort-Aznar, Gareth Evans, Sangeeta Chawla, Sean T. Sweeney
bioRxiv 2020.06.05.136622; doi: https://doi.org/10.1101/2020.06.05.136622

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