Shahani Neelam, Sawa Akira
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Biochim Biophys Acta. 2012 Jun;1820(6):736-42. doi: 10.1016/j.bbagen.2011.07.010. Epub 2011 Jul 23.
One of the signaling mechanisms mediated by nitric oxide (NO) is through S-nitrosylation, the reversible redox-based modification of cysteine residues, on target proteins that regulate a myriad of physiological and pathophysiological processes. In particular, an increasing number of studies have identified important roles for S-nitrosylation in regulating cell death.
The present review focuses on different targets and functional consequences associated with nitric oxide and protein S-nitrosylation during neuronal cell death.
S-Nitrosylation exhibits double-edged effects dependent on the levels, spatiotemporal distribution, and origins of NO in the brain: in general Snitrosylation resulting from the basal low level of NO in cells exerts anti-cell death effects, whereas S-nitrosylation elicited by induced NO upon stressed conditions is implicated in pro-cell death effects.
Dysregulated protein S-nitrosylation is implicated in the pathogenesis of several diseases including degenerative diseases of the central nervous system (CNS). Elucidating specific targets of S-nitrosylation as well as their regulatory mechanisms may aid in the development of therapeutic intervention in a wide range of brain diseases.
一氧化氮（NO）介导的信号传导机制之一是通过S-亚硝基化，即基于氧化还原的半胱氨酸残基的可逆修饰，作用于调节众多生理和病理生理过程的靶蛋白。特别是，越来越多的研究已经确定S-亚硝基化在调节细胞死亡中起重要作用。
本综述重点关注神经元细胞死亡过程中与一氧化氮和蛋白质S-亚硝基化相关的不同靶点和功能后果。
S-亚硝基化表现出双刃剑效应，这取决于大脑中NO的水平、时空分布和来源：一般来说，细胞中基础低水平的NO导致的S-亚硝基化发挥抗细胞死亡作用，而应激条件下诱导产生的NO引发的S-亚硝基化则与促细胞死亡作用有关。
蛋白质S-亚硝基化失调与包括中枢神经系统（CNS）退行性疾病在内的几种疾病的发病机制有关。阐明S-亚硝基化的特定靶点及其调节机制可能有助于开发针对多种脑部疾病的治疗干预措施。
