Calabrese V, Bates T E, Stella A M
Department of Chemistry, Faculty of Medicine, University of Catania, Italy.
Neurochem Res. 2000 Oct;25(9-10):1315-41. doi: 10.1023/a:1007604414773.
Nitric oxide and other reactive nitrogen species appear to play several crucial roles in the brain. These include physiological processes such as neuromodulation, neurotransmission and synaptic plasticity, and pathological processes such as neurodegeneration and neuroinflammation. There is increasing evidence that glial cells in the central nervous system can produce nitric oxide in vivo in response to stimulation by cytokines and that this production is mediated by the inducible isoform of nitric oxide synthase. Although the etiology and pathogenesis of the major neurodegenerative and neuroinflammatory disorders (Alzheimer's disease, amyothrophic lateral sclerosis, Parkinson's disease, Huntington's disease and multiple sclerosis) are unknown, numerous recent studies strongly suggest that reactive nitrogen species play an important role. Furthermore, these species are probably involved in brain damage following ischemia and reperfusion, Down's syndrome and mitochondrial encephalopathies. Recent evidence also indicates the importance of cytoprotective proteins such as heat shock proteins (HSPs) which appear to be critically involved in protection from nitrosative and oxidative stress. In this review, evidence for the involvement of nitrosative stress in the pathogenesis of the major neurodegenerative/ neuroinflammatory diseases and the mechanisms operating in brain as a response to imbalance in the oxidant/antioxidant status are discussed.
一氧化氮和其他活性氮物质似乎在大脑中发挥着多种关键作用。这些作用包括神经调节、神经传递和突触可塑性等生理过程，以及神经退行性变和神经炎症等病理过程。越来越多的证据表明，中枢神经系统中的胶质细胞能够在体内对细胞因子的刺激产生一氧化氮，并且这种产生是由一氧化氮合酶的诱导型同工型介导的。尽管主要的神经退行性和神经炎症性疾病（阿尔茨海默病、肌萎缩侧索硬化症、帕金森病、亨廷顿舞蹈病和多发性硬化症）的病因和发病机制尚不清楚，但最近的大量研究强烈表明活性氮物质起着重要作用。此外，这些物质可能参与了缺血再灌注、唐氏综合征和线粒体脑病后的脑损伤。最近的证据还表明了细胞保护蛋白如热休克蛋白（HSPs）的重要性，它们似乎在抵御亚硝化和氧化应激中起着关键作用。在这篇综述中，我们讨论了亚硝化应激参与主要神经退行性/神经炎症性疾病发病机制的证据，以及大脑中作为对氧化还原状态失衡的一种反应而发挥作用的机制。
