Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer's disease
Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer's disease
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DOI：
10.1016/s0197-4580(03)00117-9
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
DeCarli, C
中科院分区：
文献类型：
--
作者：
SantaCruz, KS;Yazlovitskaya, E;DeCarli, C
越来越多的证据支持氧化应激在阿尔茨海默病（AD）病理学中的作用。这一观点得到了最近发现的与海马AD病理学相关的NAD（P）H：醌氧化还原酶（NQO 1）活性增加的进一步支持，这是一种有效的抗氧化系统。然而，如果增加的NQO 1活性确实与AD过程相关，我们将期望在整个受影响的脑区域中看到NQO 1活性与AD病理学的区域共定位，并且在未受AD影响的区域中没有NQO 1活性。我们通过测量NQO 1酶活性和NQO 1免疫组织化学染色来检验这一假设，这些酶活性和NQO 1免疫组织化学染色通常受AD过程影响的区域如额叶皮质，并将其与通常不受AD过程影响的区域如枕叶皮质，小脑，AD患者额叶与小脑NQO 1酶活性的比值显著增加，（2.07 +/- 1.90）与对照组（0.60 +/- 0.31; P < 0.03）。此外，区域免疫组织化学染色显示NQO 1染色的特定定位的星形胶质细胞和神经突起周围的老年斑。免疫组织化学染色的程度也密切相关的程度，局部AD病理检查的各个脑区。神经元NQO 1染色在额叶皮质的AD患者是不存在的对照额叶皮质，但被发现在相同程度上在神经元的黑质的AD患者和controls.We的结论是NQO 1活性co-localizes密切与AD病理支持一个假定的作用，作为一个抗氧化系统上调响应于AD过程中的氧化应激。NQO 1的抗氧化作用进一步得到了AD患者和对照组的黑质神经元中神经元NQO 1活性增加的支持，因为已知该神经元群体处于恒定的氧化应激下。虽然需要进一步的研究，这些发现，结合以前的工作，表明增加NQO 1活性可能是神经保护，可能提供新的见解AD的病理生理学，也可能为未来的治疗提供可能的途径。(C)2003年爱思唯尔公司All rights reserved.
Converging evidence supports the role of oxidative stress in the pathology of Alzheimer's disease (AD). This notion is further supported by recent findings of increased NAD(P)H:quinone oxidodreductase (NQO1) activity, a potent antioxidant system, in association with hippocampal AD pathology. If increased NQO1 activity is truly related to the AD process, however, we would expect to see regional co-localization of NQO1 activity with AD pathology throughout affected brain regions and the absence of NQO1 activity in regions unaffected by AD. We examined this hypothesis by measuring NQO1 enzymatic activity and NQO1 immunohistochemical staining in regions commonly affected by the AD process such as frontal cortex and compared this to regions generally unaffected by the AD process such as occipital cortex, cerebellum, and substantia nigra for a group of AD patients and controls.The ratio of frontal to cerebellar NQO1 enzymatic activity was significantly increased in patients with AD (2.07 +/- 1.90) versus controls (0.60 +/- 0.31; P < 0.03). Moreover, regional immunohistochemical staining revealed specific localization of NQO1 staining to astrocytes and neurites surrounding senile plaques. The extent of immunohistochemical staining also closely correlated with the extent of local AD pathology across the various brain regions examined. Neuronal NQO1 staining seen in frontal cortex of AD patients was absent in frontal cortex of controls, but was found to the same extent in neurons of the substantia nigra of both AD patients and controls.We conclude that NQO1 activity co-localizes closely with AD pathology supporting a presumed role as an antioxidant system upregulated in response to the oxidative stress of the AD process. The antioxidant role for NQO1 is further supported by finding increased neuronal NQO1 activity in substantia nigra neurons of both AD patients and controls as this neuronal population is known to be under constant oxidative stress. While requiring further study, these findings, in conjunction with previous work, suggest that increased NQO1 activity may be neuroprotective, may offer novel insights into the pathophysiology of AD and may also provide possible avenues for future treatment. (C) 2003 Elsevier Inc. All rights reserved.