JNK signalling regulates antioxidant responses in neurons.

JNK signalling regulates antioxidant responses in neurons.
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DOI:
10.1016/j.redox.2020.101712
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发表时间:
2020-10
期刊:
影响因子:
11.4
通讯作者:
Sweeney ST
Sweeney ST
中科院分区:
生物学1区
文献类型:
--
作者:
Ugbode C;Garnham N;Fort-Aznar L;Evans GJO;Chawla S;Sweeney ST

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活性氧(ROS)是在突触活动的生理发作期间产生的,并且是中枢神经系统中病理条件的结果。神经元如何在这些不同的环境中响应和区分ROS目前尚不清楚。在具有增强的JNK活性的果蝇突变体中,观察到较低水平的ROS,并且这些动物对ROS的变化和由氧化应激诱导的突触形态的变化都具有抗性。在野生型果蝇中,破坏JNK-AP-1信号传导扰乱氧化还原稳态,表明JNK活性正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设,发现JNK活性以c-Jun依赖性方式调节抗氧化基因Srxn-1的表达。我们描述了一个保守的“适应性”的作用,神经元JNK在维持氧化还原稳态,是相关的几种神经退行性疾病。
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.
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