Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease.
Evaluation of coenzyme Q as an antioxidant strategy for Alzheimer's disease.
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DOI：
10.3233/jad-2008-14210
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
T. Wadsworth;James A Bishop;A. Pappu;R. Woltjer;J. Quinn
中科院分区：
文献类型：
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作者：
T. Wadsworth;James A Bishop;A. Pappu;R. Woltjer;J. Quinn
越来越多的证据表明，阿尔茨海默病(AD)与氧化损伤有关，氧化损伤部分是由线粒体功能障碍引起的。在这里，我们研究了用线粒体抗氧化剂辅酶Q(CoQ)改善阿尔茨海默病病理的可行性。外源性辅酶Q以浓度依赖的方式保护MC65神经母细胞瘤细胞免受淀粉样β蛋白前体C末端片段(APP CTF)诱导的神经毒性，6.25微米或更高的浓度提供了近乎完全的保护。C65/BL6小鼠在饮食中补充辅酶Q，剂量为10g/kg，持续一个月，显著抑制了大脑蛋白质羰基水平，这是氧化损伤的标志。2g洛伐他汀/kg饮食干预辅酶Q合成治疗1个月后，脑辅酶Q10水平显著降低。辅酶Q或洛伐他汀治疗均不影响线粒体能量学(脑ATP水平和线粒体膜电位)。我们的结果表明，口服辅酶Q可能是治疗神经退行性疾病的一种可行的抗氧化策略。我们的数据支持在AD动物模型上进行辅酶Q试验，以确定是否有必要进行临床试验。
Increasing evidence suggests that Alzheimer's disease (AD) is associated with oxidative damage that is caused in part by mitochondrial dysfunction. Here we investigated the feasibility of modifying Alzheimer pathology with the mitochondrial antioxidant coenzyme Q (CoQ). Exogenous CoQ protected MC65 neuroblastoma cells from amyloid-beta protein precursor C-terminal fragment (APP CTF)-induced neurotoxicity in a concentration dependent manner, with concentrations of 6.25 microM and higher providing near complete protection. Dietary supplementation with CoQ at a dose of 10 g/kg diet to C65/Bl6 mice for one month significantly suppressed brain protein carbonyl levels, which are markers of oxidative damage. Treatment for one month with 2 g lovastatin/kg diet, which interferes with CoQ synthesis, resulted in a significant lowering of brain CoQ10 levels. Mitochondrial energetics (brain ATP levels and mitochondrial membrane potential) were unaffected by either CoQ or lovastatin treatment. Our results suggest that oral CoQ may be a viable antioxidant strategy for neurodegenerative disease. Our data supports a trial of CoQ in an animal model of AD in order to determine whether a clinical trial is warranted.