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阿尔茨海默病患者脑脊液中还原型和氧化型辅酶 Q-10 及 8-羟基-2'-脱氧鸟苷的水平表明,线粒体氧化损伤和/或氧化 DNA 损伤有助于神经退行性过程。

Levels of reduced and oxidized coenzyme Q-10 and 8-hydroxy-2'-deoxyguanosine in the CSF of patients with Alzheimer's disease demonstrate that mitochondrial oxidative damage and/or oxidative DNA damage contributes to the neurodegenerative process.

机构信息

Department of Neurology, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-0805, Japan.

出版信息

J Neurol. 2010 Mar;257(3):399-404. doi: 10.1007/s00415-009-5333-x. Epub 2009 Sep 27.

Abstract

To investigate the possibility that mitochondrial oxidative damage, oxidative DNA damage or both contribute to the neurodegenerative process of Alzheimer's disease (AD), we employed high-performance liquid chromatography using an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q-10 (CoQ-10) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 30 patients with AD and in 30 age-matched controls with no neurological disease. The percentage of oxidized/total CoQ-10 (%CoQ-10) in the CSF of the AD group (78.2 +/- 18.8%) was significantly higher than in the control group (41.3 +/- 10.4%) (P < 0.0001). The concentration of 8-OHdG in the CSF of AD patients was greater than in the CSF of controls (P < 0.0001) and was positively correlated with the duration of illness (r(s) = 0.95, P < 0.0001). The %CoQ-10 was correlated with concentrations of 8-OHdG in the CSF of AD patients (r(s) = 0.66, P < 0.001). The present study suggests that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of early AD development.

摘要

为了研究线粒体氧化损伤、氧化 DNA 损伤或两者都对阿尔茨海默病(AD)神经退行性过程的贡献的可能性,我们采用高效液相色谱法结合电化学检测器,测量了 30 例 AD 患者和 30 例年龄匹配的无神经疾病对照者脑脊液(CSF)中辅酶 Q-10(CoQ-10)的还原和氧化形式及 8-羟基-2'-脱氧鸟苷(8-OHdG)的浓度。AD 组 CSF 中氧化/总 CoQ-10(%CoQ-10)的百分比(78.2 +/- 18.8%)明显高于对照组(41.3 +/- 10.4%)(P < 0.0001)。AD 患者 CSF 中的 8-OHdG 浓度高于对照组(P < 0.0001),且与疾病持续时间呈正相关(r(s) = 0.95,P < 0.0001)。%CoQ-10 与 AD 患者 CSF 中的 8-OHdG 浓度呈正相关(r(s) = 0.66,P < 0.001)。本研究表明,线粒体氧化损伤和氧化 DNA 损伤在 AD 早期发病机制中均发挥重要作用。

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