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阿尔茨海默病中的 S-亚硝基化。

S-Nitrosylation in Alzheimer's disease.

机构信息

Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China.

出版信息

Mol Neurobiol. 2015 Feb;51(1):268-80. doi: 10.1007/s12035-014-8672-2. Epub 2014 Mar 25.

Abstract

S-Nitrosylation, a redox-mediated posttranslational modification, is a result of the covalent binding nitric oxide (NO)-related species to cysteine residues of target proteins with the formation of nitrosothiols (SNOs). Normally, protein S-nitrosylation could be a cellular signaling mechanism, as is often a reversible and selective process, akin to protein phosphorylation. Emerging evidences have certified that the occurrence of aberrant S-nitrosylation of protein reactions could lead to protein misfolding, mitochondrial fission, synaptic damage, or apoptosis, thus contributing to the pathogenesis of Alzheimer's disease (AD). In this review, we summarize the recent findings of key S-nitrosylated proteins which play crucial roles in the pathogenesis of AD and discuss how SNO proteins affect the progression of AD. In addition, it has been demonstrated that interference of S-nitrosylation could potentially protect from mitochondrial dysfunction, synaptic loss, or neuronal cell death in AD animal models. Hence, we also present the recent advances and challenges in targeting S-nitrosylated proteins for AD therapies.

摘要

S-亚硝基化作用是一种氧化还原介导的翻译后修饰,是一氧化氮(NO)相关物质与靶蛋白中半胱氨酸残基的共价结合形成亚硝硫醇(SNOs)的结果。通常,蛋白质 S-亚硝基化作用可以作为一种细胞信号机制,通常是一个可逆和选择性的过程,类似于蛋白质磷酸化。新出现的证据证明,蛋白质反应中异常 S-亚硝基化的发生可能导致蛋白质错误折叠、线粒体分裂、突触损伤或细胞凋亡,从而导致阿尔茨海默病(AD)的发病机制。在这篇综述中,我们总结了在 AD 发病机制中起关键作用的关键 S-亚硝基化蛋白的最新发现,并讨论了 SNO 蛋白如何影响 AD 的进展。此外,已经证明,干扰 S-亚硝基化作用可能有助于防止 AD 动物模型中的线粒体功能障碍、突触丧失或神经元细胞死亡。因此,我们还介绍了针对 AD 治疗靶向 S-亚硝基化蛋白的最新进展和挑战。

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