Oxidative stress in brain aging - Implications for therapeutics of neurodegenerative diseases
Oxidative stress in brain aging - Implications for therapeutics of neurodegenerative diseases
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DOI：
10.1016/s0197-4580(02)00019-2
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发表时间：
2002-09-01
影响因子：
4.2
通讯作者：
Hensley, K
中科院分区：
文献类型：
--
作者：
Floyd, RA;Hensley, K
年龄对神经退行性疾病的易感性有很大的影响，包括中风和认知障碍(CI)的易感性，即使在健康状况最好的人中也是如此。我们对氧化应激在老化的大脑中增加这一概念进行了批判性评估。严格的研究表明，氧化蛋白和氧化DNA损伤随年龄的增加呈对数增长。抗氧化保护酶活性的降低并不是观察到的增加的原因。脂质氧化产物4-羟基-2-壬烯醛(HNE)与线粒体关键酶的反应性可能在能量产生的年龄依赖性丧失和神经元对凋亡的敏感性增加中起重要作用。年龄依赖性增强的神经炎性过程可能在神经退行性疾病中导致神经元死亡或功能障碍的毒素产生中发挥重要作用。非类固醇抗炎药(NSAIDs)显示出巨大的前景。补充维生素E对认知功能没有明显的有益影响。涉及环氧合酶-II(COX II)抑制剂和淀粉样β蛋白疫苗接种的阿尔茨海默病(AD)的主要临床试验已经停止。基于阻断神经元损伤神经炎症过程的新疗法在减缓痴呆进展方面显示出巨大的希望，尽管它们尚未进入临床实践。(C)2002 Elsevier Science Inc.保留所有权利。
Age has a powerful effect on enhanced susceptibility to neurodegenerative diseases, including susceptibility to stroke and cognitive impairment (CI) even in optimally healthy individuals. We critically evaluated the notion that oxidative stress increases in aging brain. Rigorous studies show logarithmic age-dependent increases in oxidized proteins and oxidized DNA lesions. Decreased activity of antioxidant protective enzymes does not account for the observed increases. The reactivity of the lipid oxidation product 4-hydroxy-2-nonenal (HNE) with key mitochondria enzymes may be important in the age-dependent loss in energy generation and enhanced susceptibility of neurons to apoptosis. Age-dependent enhanced neuroinflammatory processes may play an important role in toxin generation that causes death or dysfunction of neurons in neurodegenerative diseases. Non-steroidal anti-inflammatory drugs (NSAIDs) show significant promise. Vitamin E supplementation did not show major beneficial effect on cognitive functions. Major clinical trials for Alzheimer's disease (AD) involving cycloxygenase-II (COX II) inhibitors and amyloid-beta vaccination have been discontinued. Novel therapeutics based on blocking neuron damaging neuroinflammatory processes show great promise for abating dementia progression although they have yet to make it to clinical practice. (C) 2002 Elsevier Science Inc. All rights reserved.