van Muiswinkel F L, de Vos R A I, Bol J G J M, Andringa G, Jansen Steur E N H, Ross D, Siegel D, Drukarch B
Department of Medical Pharmacology, Institute for Clinical and Experimental Neurosciences (ICEN), VU University Medical Center, Vrije Universiteit, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Neurobiol Aging. 2004 Oct;25(9):1253-62. doi: 10.1016/j.neurobiolaging.2003.12.010.
Dopamine (DA) autooxidation, and consequent formation of neurotoxic DA-derived quinones and reactive oxygen species, has been implicated in dopaminergic cell death and, hence, in the pathogenesis of Parkinson's disease (PD). Stimulation of pathways involved in the detoxication of DA-quinones in the brain is hypothesized to be an effective means to limit oxidative stress and to confer neuroprotection in PD. In this respect, the inducible flavoprotein NAD(P)H:quinone oxidoreductase (NQO1) is of particular interest as it is directly implicated in the detoxication of DA-quinones and, in addition, has broad spectrum anti-oxidant properties. To study the potential pathophysiological role of NQO1 in PD, the cellular expression of NQO1 was examined in the mesencephalon of PD patients and age-matched controls. In the substantia nigra pars compacta (SNpc), NQO1 was found to be expressed in astroglial and endothelial cells and, albeit less frequently, also in dopaminergic neurons. Moreover, while overt NQO1 immunoreactivity was absent in the surrounding nervous tissue, in the Parkinsonian SNpc a marked increase in the astroglial and neuronal expression of NQO1 was consistently observed.
多巴胺（DA）的自动氧化以及由此产生的神经毒性DA衍生醌类和活性氧物质，被认为与多巴胺能细胞死亡有关，因此也与帕金森病（PD）的发病机制有关。据推测，刺激大脑中参与DA-醌解毒的途径是限制氧化应激并在PD中提供神经保护的有效手段。在这方面，可诱导的黄素蛋白NAD(P)H：醌氧化还原酶（NQO1）特别受关注，因为它直接参与DA-醌的解毒，此外还具有广谱抗氧化特性。为了研究NQO1在PD中的潜在病理生理作用，我们检测了PD患者和年龄匹配对照组中脑NQO1的细胞表达。在黑质致密部（SNpc）中，发现NQO1在星形胶质细胞和内皮细胞中表达，尽管频率较低，但在多巴胺能神经元中也有表达。此外，虽然周围神经组织中没有明显的NQO1免疫反应性，但在帕金森病的SNpc中，始终观察到星形胶质细胞和神经元中NQO1的表达显著增加。
