Decreased base excision repair and increased helicase activity in Alzheimer's disease brain
Decreased base excision repair and increased helicase activity in Alzheimer's disease brain
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DOI：
10.1016/s0006-8993(99)02335-5
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发表时间：
2000-02-07
期刊：
影响因子：
2.9
通讯作者：
Markesbery, WR
中科院分区：
文献类型：
--
作者：
Lovell, MA;Xie, CS;Markesbery, WR
最近的研究表明，在阿尔茨海默病 (AD) 中，大脑和脑脊液 (CSF) 中的 DNA 氧化增加，并且 CSF 中的游离修复产物水平降低。这是一项对来自 10 AD 和 8 名年龄匹配对照受试者的四个大脑区域的核蛋白样本中碱基切除修复酶、8-氧鸟嘌呤糖基酶（负责切除 8-氧鸟嘌呤）和 DNA 解旋酶活性的研究。在 AD 海马和海马旁回 (HPG)、颞上回和中回 (SMTG) 以及顶下小叶 (SPL) 的核部分中观察到 8-氧代鸟嘌呤糖基化酶活性显着降低 (p < 0.05)。除 IPL 外，所有核样品中的 DNA 解旋酶活性均升高，其中 HPG 和 CER 显着升高，在 AD IPL 的核级分中观察到解旋酶活性统计显着性降低。我们的结果表明，AD 中 8-氧代鸟嘌呤的修复能力下降。 AD 患者某些脑区 DNA 解旋酶活性的适度增加可能会干扰碱基切除修复机制。总体而言，DNA 损伤修复的减少可能与 AD 神经变性的发病机制有关。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Recent studies show an increase in DNA oxidation in brain and cerebrospinal fluid (CSF), and decreased levels of the free repair product in CSF in Alzheimer's disease (AD). This is a study of the activity of the base excision repair enzyme, 8-oxoguanine glycosylase (responsible for the excision of 8-oxoguanine), and DNA helicase activity in nuclear protein samples from four brain regions of 10 AD and eight age-matched control subjects. Statistically significant(p < 0.05) decreases in 8-oxoguanine glycosylase activity were observed in the nuclear fraction of AD hippocampal and parahippocampal gyri (HPG), superior and middle temporal gyri (SMTG), and inferior parietal lobule (SPL). DNA helicase activity was elevated in all nuclear samples except the IPL with statistically significant elevations in the HPG and CER, Statistically significant depletion of helicase activity was observed in the nuclear fraction in AD IPL. Our results demonstrate that the repair capabilities for 8-oxoguanine are decreased in AD. The modest increase in DNA helicase activity in some brain regions in AD may interfere with base excision repair mechanisms. Overall, the decreased repair of DNA damage could be involved in the pathogenesis of neurodegeneration in AD. (C) 2000 Elsevier Science B.V. All rights reserved.