JNK signalling regulates antioxidant responses in neurons

JNK signalling regulates antioxidant responses in neurons
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JNK 信号调节神经元的抗氧化反应

DOI:
10.1101/2020.06.05.136622
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发表时间:
2020
期刊:
--
影响因子:
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通讯作者:
Ugbode C
Ugbode C
中科院分区:
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作者:
Ugbode C

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活性氧种(ROS)是在突触活动的生理性发作中产生的,是中枢神经系统病理条件的结果。神经元如何在这些不同的环境中对RO做出反应和区分RO目前尚不清楚。在JNK活性增强的果蝇突变体中,观察到较低水平的ROS,这些动物对氧化应激引起的ROS变化和突触形态的变化都具有抵抗力。在野生型果蝇中,扰乱JNK-AP-1信号的氧化还原动态平衡表明JNK活性积极地调节神经元的抗氧化防御。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依赖的方式调节抗氧化剂基因Srxn-1的表达。我们描述了神经元JNK在维持氧化还原稳态中的保守的“适应性”作用,这与几种神经退行性疾病有关。
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. InDrosophilamutants 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 geneSrxn-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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