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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.

SUBMITTER: Ugbode C

PROVIDER: S-EPMC7502373 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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JNK signalling regulates antioxidant responses in neurons.

Ugbode Chris C Garnham Nathan N Fort-Aznar Laura L Evans Gareth J O GJO Chawla Sangeeta S Sweeney Sean T ST

Redox biology 20200904

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, disrupt ...[more]

PMID: 32949970

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