Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse.
Nitric Oxide-Mediated Posttranslational Modifications: Impacts at the Synapse.
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DOI：
10.1155/2016/5681036
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发表时间：
2016
影响因子：
--
通讯作者：
Steinert JR
中科院分区：
文献类型：
--
作者：
Bradley SA;Steinert JR
一氧化氮（NO）是一种重要的气体递质分子，参与整个神经系统的许多生理过程。除了参与生理可塑性过程（长期增强，LTP；长期抑制，LTD）（包括 NMDAR 介导的神经元一氧化氮合酶（nNOS）的钙依赖性激活）之外，最近还出现了对氮能信号传导的生理和病理后果的新见解。除了典型的 cGMP 介导的信号传导之外，NO 还涉及许多涉及翻译后修饰的途径。在这篇综述中，我们讨论了 S-亚硝基化和 3-硝基酪氨酸化对具有潜在功能调节作用的蛋白质的多重影响，但将分析限制在涉及突触传递和囊泡释放的信号传导。在这里，介导突触传递的关键蛋白质可以经历突触前或突触后起源的翻译后修饰。在正常的大脑功能过程中，这两条通路都是重要的细胞信号级联，调节一系列不同的生理过程，包括突触可塑性、转录活动和神经元存活。相比之下，有证据表明衰老和疾病会通过过量的一氧化氮产生而诱发亚硝化应激。因此，不受控制的 S-亚硝基化/3-硝基酪氨酸化可能会发生，并代表导致各种神经退行性疾病（包括帕金森氏症、阿尔茨海默氏症和亨廷顿氏症）发病和进展的病理特征。
Nitric oxide (NO) is an important gasotransmitter molecule that is involved in numerous physiological processes throughout the nervous system. In addition to its involvement in physiological plasticity processes (long-term potentiation, LTP; long-term depression, LTD) which can include NMDAR-mediated calcium-dependent activation of neuronal nitric oxide synthase (nNOS), new insights into physiological and pathological consequences of nitrergic signalling have recently emerged. In addition to the canonical cGMP-mediated signalling, NO is also implicated in numerous pathways involving posttranslational modifications. In this review we discuss the multiple effects of S-nitrosylation and 3-nitrotyrosination on proteins with potential modulation of function but limit the analyses to signalling involved in synaptic transmission and vesicular release. Here, crucial proteins which mediate synaptic transmission can undergo posttranslational modifications with either pre- or postsynaptic origin. During normal brain function, both pathways serve as important cellular signalling cascades that modulate a diverse array of physiological processes, including synaptic plasticity, transcriptional activity, and neuronal survival. In contrast, evidence suggests that aging and disease can induce nitrosative stress via excessive NO production. Consequently, uncontrolled S-nitrosylation/3-nitrotyrosination can occur and represent pathological features that contribute to the onset and progression of various neurodegenerative diseases, including Parkinson's, Alzheimer's, and Huntington's.