Weill Cornell Medical College, Department of Neurology and Neuroscience, 525 East 68th Street, New York, NY 10065, USA.
Neurosci Lett. 2011 Apr 4;492(3):150-4. doi: 10.1016/j.neulet.2011.01.077. Epub 2011 Feb 12.
In addition to mitochondria, NADPH oxidase (NOX) is a source of oxidative stress, which can induce oxidative damage in Alzheimer's disease (AD). For this reason, several groups have investigated the effect of its inhibition. In AD mice, NADPH oxidase 2 (NOX2) deficiency improved behavior and cerebrovascular function, and reduced oxidative stress. In our study, we administered the NOX inhibitor apocynin to Tg19959 mice, and found that it did not improve cognitive and synaptic deficits, and did not decrease amyloid deposition, microgliosis and hyperphosphorylated tau. However, apocynin reduced carbonyl levels in the cerebral cortex but not the hippocampus, which may have not been sufficient to ameliorate symptoms. Also, the reduction of NOX-mediated oxidative stress may not be sufficient to prevent AD, since other sources of reactive oxygen species such as mitochondria may be more important.
除了线粒体,NADPH 氧化酶(NOX)也是氧化应激的一个来源,它会导致阿尔茨海默病(AD)的氧化损伤。出于这个原因,有几个研究小组研究了抑制其的效果。在 AD 小鼠中,NADPH 氧化酶 2(NOX2)缺乏症改善了行为和脑血管功能,并减少了氧化应激。在我们的研究中,我们给 Tg19959 小鼠施用了 NOX 抑制剂 apocynin,但发现它没有改善认知和突触缺陷,也没有减少淀粉样蛋白沉积、小胶质细胞增生和过度磷酸化的 tau。然而,apocynin 降低了大脑皮层中的羰基水平,但没有降低海马体中的羰基水平,这可能不足以改善症状。此外,NOX 介导的氧化应激的减少可能不足以预防 AD,因为线粒体等其他活性氧的来源可能更为重要。