JNK 信号通路调节神经元中的抗氧化反应。

JNK signalling regulates antioxidant responses in neurons.

机构信息

Department of Biology, University of York, York, YO10 5DD, UK; York Biomedical Research Institute, University of York, York, YO10 5DD, UK.

出版信息

Redox Biol. 2020 Oct;37:101712. doi: 10.1016/j.redox.2020.101712. Epub 2020 Sep 4.

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.

活性氧 (ROS) 在生理突触活动期间产生，并且是中枢神经系统中病理状况的结果。神经元如何在这些不同的情况下对 ROS 作出反应并加以区分目前尚不清楚。在 JNK 活性增强的果蝇突变体中，观察到 ROS 水平较低，这些动物对 ROS 的变化以及氧化应激引起的突触形态变化均具有抗性。在野生型果蝇中，破坏 JNK-AP-1 信号会破坏氧化还原平衡，表明 JNK 活性正向调节神经元抗氧化防御。我们在哺乳动物神经元中验证了这一假说，发现 JNK 活性以 c-Jun 依赖的方式调节抗氧化基因 Srxn-1 的表达。我们描述了神经元 JNK 在维持氧化还原平衡中的保守“适应性”作用，这与几种神经退行性疾病有关。