Study of 3-nitrotyrosine in the cerebrospinal fluid in neurodegenerative disorders

为探讨一氧化氮（NO）神经元死亡在衰老和帕金森病（PD）、阿尔茨海默病（AD）、肌萎缩侧索硬化症（ALS）、脊髓小脑变性（OPCA和CCA）中的意义，测定PD、AD、ALS、OPCA、CCA患者及神经正常对照脑脊液中3-硝基酪氨酸和酪氨酸的浓度。随着年龄的增长，3-硝基酪氨酸浓度和3-硝基酪氨酸/酪氨酸比值显著升高。AD和ALS患者的3-硝基酪氨酸浓度和3-硝基酪氨酸/酪氨酸比值显著高于同龄对照（7倍）和ALS（约6倍）。PD、AD、ALS、OPCA和cca患者的酪氨酸浓度均无变化。在AD患者中，3-硝基酪氨酸浓度和3-硝基酪氨酸/酪氨酸比值随着认知功能的下降而显著升高，而酪氨酸浓度没有变化。这些发现提示，酪氨酸硝化的激活、硝化酪氨酸含蛋白的增加和/或其降解可能参与脑老化，并在AD和ALS的发病机制中发挥重要作用。

To investigate the significance of nitric oxide (NO) neuron death in aging and Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and spinocerebellar degeneration (OPCA and CCA), the concentrations of 3-nitrotyrosine and tyrosine in the cerebrospinal fluid were determined in patients with PD, AD, ALS, OPCA, CCA and neurologically normal controls.1. The 3-nitrotyrosine concentration and the 3-nitrotyrosme/tyrosme ratio significantly increased with advancing age.2. The 3-nitrotyrosine concentrations and the 3-nitrotyrosine/tyrosine ratios increased significantly compared with controls of similar age in patients with AD (seven-fold) and ALS (approximately six-fold).3. The tyrosine concentrations were unaltered in all patients with PD, AD, ALS, OPCA and CCA.4. In patients with AD, the 3-nitrotyrosine concentration and the 3-nitrotyrosine/tyrosine ratio increased significantly with decreasing cognitive functions, whereas the tyrosine concentration did not change.These findings suggest that an activation of tyrosine nitration, increase in nitrated tyrosine-containing proteins, and / or its degradation may be involved in brain aging and play an important role in the pathogenesis of AD and ALS.