Expression of 8-oxoguanine DNA glycosylase is reduced and associated with neurofibrillary tangles in Alzheimer's disease brain

被引：120

作者：

Iida, T ^{[1
]}

Furuta, A

Nishioka, K

Nakabeppu, Y

Iwaki, T

机构：

[1] Kyushu Univ 60, Grad Sch Med Sci, Inst Neurol, Dept Neuropathol, Fukuoka 8128582, Japan

[2] Kyushu Univ, Med Inst Bioregulat, Dept Biochem, Fukuoka 8128582, Japan

[3] Japan Sci & Technol Corp, CREST, Tokyo, Japan

来源：

ACTA NEUROPATHOLOGICA | 2002年 / 103卷 / 01期

关键词：

Alzheimer's disease; oxidative DNA damage; 8-oxo-2 '-deoxyguanosine; 8-oxoguanine DNA glycosylase (hOGG1) immunohistochemistry;

D O I：

10.1007/s004010100418

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Recent studies have confirmed the role of reactive oxygen species in the pathogenesis of Alzheimer's disease (AD). 8-Oxo-2'-deoxyguanosine accumulation in AD brain has been discussed, but few studies of DNA repair enzymes in AD brain have been done. Further, a relationship between mitochondrial function and oxidative stress has been noticed. In this study, to evaluate the repair mechanism for oxidative DNA damage in AD brain, we investigated brain tissues from autopsy cases of AD and control cases using an antibody against the mitochondrial form of 8-oxoguanine DNA glycosylase (hOGG1-2a), an enzyme that repairs 8-oxo-2'-deoxyguanosine. hOGG1-2a is expressed mainly in the neuronal cytoplasm in both AD and control cases in regionally different manners. Expression of hOGG1-2a is decreased in the orbitofrontal gyrus and entorhinal cortex in AD compared to that in control cases. Immunoreactivity to hOGG1-2a is associated with neurofibrillary tangles, dystrophic neurites and reactive astrocytes in AD. Our results indicate that the repair enzyme for oxidative damage in mitochondrial DNA may not function appropriately in AD, and thus oxidative DNA damage in mitochondria may be involved in the pathomechanism of AD.

引用

页码：20 / 25

页数：6

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