JNK signalling regulates antioxidant responses in neurons
JNK signalling regulates antioxidant responses in neurons
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.
Garnham Nathan、Fort-Aznar Laura、Evans Gareth、Ugbode Chris、Chawla Sangeeta、Sweeney Sean T.
Department of Biology, University of York||York Biomedical Research Institute, University of YorkDepartment of Biology, University of York||York Biomedical Research Institute, University of YorkDepartment of Biology, University of York||York Biomedical Research Institute, University of YorkDepartment of Biology, University of York||York Biomedical Research Institute, University of YorkDepartment of Biology, University of York||York Biomedical Research Institute, University of YorkDepartment of Biology, University of York||York Biomedical Research Institute, University of York
神经病学、精神病学生理学生物化学
DrosophilaGlutathioneHydrogen PeroxideROS
Garnham Nathan,Fort-Aznar Laura,Evans Gareth,Ugbode Chris,Chawla Sangeeta,Sweeney Sean T..JNK signalling regulates antioxidant responses in neurons[EB/OL].(2025-03-28)[2025-05-25].https://www.biorxiv.org/content/10.1101/2020.06.05.136622.点此复制
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