Nitric Oxide Homeostasis in Neurodegenerative Diseases
Nitric Oxide Homeostasis in Neurodegenerative Diseases
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DOI：
10.2174/1567205012666150921101250
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发表时间：
2016-01-01
影响因子：
2.1
通讯作者：
Hannibal, Luciana
中科院分区：
文献类型：
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作者：
Hannibal, Luciana
多年来，一氧化氮在帕金森病和阿尔茨海默病等神经退行性疾病的发病机制和进展中的作用已变得越来越突出。产生活性氧的酶活性增加、抗氧化酶活性降低以及谷胱甘肽库失衡介导和标记了神经退行性过程。蛋白质的大部分氧化损伤是由一氧化氮合酶 (NOS) 过量产生一氧化氮及其随后与活性氧的反应引起的。蛋白质组学方法通过促进蛋白质差异表达模式和氧化修饰的定量评估以及绘制其非规范功能，极大地推进了该领域的发展。作为参与多种生化途径的信号分子，一氧化氮的水平受到严格的调节。所有三种 NOS 亚型在阿尔茨海默病中均表现出异常的表达模式，改变细胞内信号传导并将氧化应激传递至未复合的方向。本综述讨论了控制一氧化氮生物合成的主要因素、反应足迹以及对神经退行性疾病发展的后续影响。
The role of nitric oxide in the pathogenesis and progression of neurodegenerative illnesses such as Parkinson's and Alzheimer's diseases has become prominent over the years. Increased activity of the enzymes that produce reactive oxygen species, decreased activity of antioxidant enzymes and imbalances in glutathione pools mediate and mark the neurodegenerative process. Much of the oxidative damage of proteins is brought about by the overproduction of nitric oxide by nitric oxide synthases ( NOS) and its subsequent reactivity with reactive oxygen species. Proteomic methods have advanced the field tremendously, by facilitating the quantitative assessment of differential expression patterns and oxidative modifications of proteins and alongside, mapping their non-canonical functions. As a signaling molecule involved in multiple biochemical pathways, the level of nitric oxide is subject to tight regulation. All three NOS isoforms display aberrant patterns of expression in Alzheimer's disease, altering intracellular signaling and routing oxidative stress in directions that are uncompounded. This review discusses the prime factors that control nitric oxide biosynthesis, reactivity footprints and ensuing effects in the development of neurodegenerative diseases.