Oxidative stress in synapse development and function
Oxidative stress in synapse development and function
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DOI：
10.1002/dneu.20957
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发表时间：
2012-01-01
影响因子：
3
通讯作者：
Sweeney, Sean T.
中科院分区：
文献类型：
--
作者：
Milton, Valerie J.;Sweeney, Sean T.
氧化应激是由活性氧化物种(ROS)水平增加引起的，被认为是衰老过程的主要贡献者。氧化应激是如何导致老化大脑的结构和功能发生变化的，目前还知之甚少。氧化应激激活了许多细胞反应，包括激活Jun-N末端激酶(JNK)途径和自噬。ROS除了起病理作用外，还起信号分子的作用。一氧化氮等ROS在学习和记忆中扮演着众所周知的角色。此外，JNK及其转录效应因子AP-1的激活也是突触功能和生长的重要调节因子。两者都是学习和记忆的生理关联的重要中介，例如长时程增强。JNK和AP-1被氧化应激激活和调节，并介导保护性细胞反应，如自噬。最近在果蝇神经肌肉接头的研究表明，自噬是通过激活JNK信号通路调节突触生长的。我们在这里概述了一个框架，通过激活JNK/AP-1和自噬，预测氧化应激是突触功能和生长的主要调节因素。我们认为，这种反应可能支持某些形式的突触生长反应和突触老化。(C)2011年威利期刊公司开发神经生物学72：100110,2012年
Oxidative stress, caused by increased levels of reactive oxidative species (ROS), is considered a major contributor to the aging process. How oxidative stress may bring about changes to structures and function in the aging brain is poorly understood. Oxidative stress activates a number of cellular responses, including activation of the Jun-N-terminal kinase (JNK) pathway and autophagy. In addition to their pathological role, ROS also act as signaling molecules. ROS such as nitric oxide have a well-known role in learning and memory. In addition, activation of JNK and its transcriptional effector AP-1 are well-known mediators of synaptic function and growth. Both are essential mediators of physiological correlates of learning and memory such as long-term potentiation. JNK and AP-1 are potently activated and regulated by oxidative stress and mediate protective cellular responses such as autophagy. Recent work at the Drosophila neuromuscular junction implicates autophagy as a regulator of synaptic growth via activation of the JNK signaling pathway. We here outline a framework predicating oxidative stress as a major regulator of synaptic function and growth by the activation of JNK/AP-1 and autophagy. Such responses, we suggest, may underpin some forms of synaptic growth responses and synaptic aging. (c) 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 100110, 2012