Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, United Kingdom.
Deakin University, The Centre for Molecular and Medical Research, School of Medicine, P.O. Box 291, Geelong, 3220, Australia.
Neurosci Biobehav Rev. 2018 Jan;84:453-469. doi: 10.1016/j.neubiorev.2017.07.017. Epub 2017 Aug 5.
There is a wealth of data indicating that de novo protein S-nitrosylation in general and protein transnitrosylation in particular mediates the bulk of nitric oxide signalling. These processes enable redox sensing and facilitate homeostatic regulation of redox dependent protein signalling, function, stability and trafficking. Increased S-nitrosylation in an environment of increasing oxidative and nitrosative stress (O&NS) is initially a protective mechanism aimed at maintaining protein structure and function. When O&NS becomes severe, mechanisms governing denitrosylation and transnitrosylation break down leading to the pathological state referred to as hypernitrosylation (HN). Such a state has been implicated in the pathogenesis and pathophysiology of several neuropsychiatric and neurodegenerative diseases and we investigate its potential role in the development and maintenance of neuroprogressive disorders. In this paper, we propose a model whereby the hypernitrosylation of a range of functional proteins and enzymes lead to changes in activity which conspire to produce at least some of the core abnormalities contributing to the development and maintenance of pathology in these illnesses.
有大量数据表明，从头蛋白质 S-亚硝基化（protein S-nitrosylation）和蛋白质转亚硝基化（protein transnitrosylation）一般介导了一氧化氮信号的大部分。这些过程使氧化还原感应成为可能，并促进了依赖于氧化还原的蛋白质信号、功能、稳定性和运输的动态平衡调节。在氧化和硝化应激（O&NS）不断增加的环境中，S-亚硝基化的增加最初是一种保护机制，旨在维持蛋白质结构和功能。当 O&NS 变得严重时，控制脱亚硝基化和转亚硝基化的机制会崩溃，导致被称为过度亚硝基化（HN）的病理状态。这种状态与多种神经精神和神经退行性疾病的发病机制和病理生理学有关，我们研究了其在神经进行性疾病的发展和维持中的潜在作用。在本文中，我们提出了一个模型，即一系列功能蛋白和酶的过度亚硝基化导致活性变化，这些变化共同导致至少部分导致这些疾病发展和维持的病理核心异常。
