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研究帕金森病中的亚硝化应激。

Studying nitrosative stress in Parkinson's disease.

作者信息

Chung Kenny K K

机构信息

Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China,

出版信息

Methods Mol Biol. 2015;1292:195-201. doi: 10.1007/978-1-4939-2522-3_14.

DOI:10.1007/978-1-4939-2522-3_14
PMID:25804757
Abstract

Parkinson's disease (PD) is marked by a selective degeneration of dopaminergic neurons in the brain stem and it is the second most common neurodegenerative disorder. The pathogenic mechanism of PD is not completely known but it is believed that oxidative stress involving the imbalance of nitric oxide (NO) signaling is involved. Recent studies have suggested that NO, through the modification of protein's cysteine residues can contribute to the pathogenesis of PD. This NO modification, designated as S-nitrosylation, is emerging as an important signaling mechanism that regulates increasing number of cellular processes such as vesicle trafficking, receptor mediated signal transduction, gene transcription, and cell death. In our studies, we found that increased nitrosative stress promotes the S-nitrosylation of neuroprotective proteins and compromises their function which contributes to the development of PD. One of the obstacles in studying S-nitrosylation signaling is how to detect this modification in biological samples. Here, two simple and commonly used methods in detecting S-nitrosylated proteins are introduced for the study of this NO signaling mechanism.

摘要

帕金森病(PD)的特征是脑干中多巴胺能神经元的选择性退化,它是第二常见的神经退行性疾病。PD的致病机制尚不完全清楚,但人们认为涉及一氧化氮(NO)信号失衡的氧化应激与之有关。最近的研究表明,NO通过修饰蛋白质的半胱氨酸残基可能促成PD的发病机制。这种被称为S-亚硝基化的NO修饰正成为一种重要的信号机制,它调节着越来越多的细胞过程,如囊泡运输、受体介导的信号转导、基因转录和细胞死亡。在我们的研究中,我们发现亚硝化应激增加会促进神经保护蛋白的S-亚硝基化并损害其功能,这有助于PD的发展。研究S-亚硝基化信号的障碍之一是如何在生物样品中检测这种修饰。在此,介绍两种用于研究这种NO信号机制的简单且常用的检测S-亚硝基化蛋白的方法。

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1
Studying nitrosative stress in Parkinson's disease.研究帕金森病中的亚硝化应激。
Methods Mol Biol. 2015;1292:195-201. doi: 10.1007/978-1-4939-2522-3_14.
2
Nitric oxide, S-nitrosylation and neurodegeneration.一氧化氮、S-亚硝基化与神经退行性变
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Oxidative and nitrosative stress in Parkinson's disease.帕金森病中的氧化应激与亚硝化应激
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S-nitrosylation in Parkinson's disease and related neurodegenerative disorders.帕金森病及相关神经退行性疾病中的S-亚硝基化作用
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S-nitrosylation of peroxiredoxin 2 promotes oxidative stress-induced neuronal cell death in Parkinson's disease.过氧化物氧化还原酶2的S-亚硝基化促进帕金森病中氧化应激诱导的神经元细胞死亡。
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Redox modulation by S-nitrosylation contributes to protein misfolding, mitochondrial dynamics, and neuronal synaptic damage in neurodegenerative diseases.氧化还原调节通过 S-亚硝基化导致神经退行性疾病中的蛋白质错误折叠、线粒体动力学和神经元突触损伤。
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