Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways.
Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways.
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DOI：
10.1089/152308603770310220
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发表时间：
2003-10
影响因子：
6.6
通讯作者：
Xiongwei Zhu;A. Raina;Hyoung-Gon Lee;M. Chao;A. Nunomura;M. Tabaton;R. Petersen;George Perry;Mark A. Smith
中科院分区：
文献类型：
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作者：
Xiongwei Zhu;A. Raina;Hyoung-Gon Lee;M. Chao;A. Nunomura;M. Tabaton;R. Petersen;George Perry;Mark A. Smith
最近的证据表明，氧化应激发生在阿尔茨海默病进展的早期，明显早于标志性病理学（即神经原纤维缠结和老年斑）的发展。异常线粒体、氧化还原过渡金属和氧化应激反应元件的相互作用有助于在患病神经元中产生活性氧。对主要细胞分子的氧化损伤可见于许多急性或慢性疾病状态，并且很明显，如果不引起恢复氧化还原平衡的补偿，细胞将迅速死亡。事实上，尽管氧化应激是阿尔茨海默病的一个突出特征，但很少有脆弱的神经元表现出明显的细胞凋亡迹象，这表明氧化应激水平并未显着超过神经元氧化防御。根据这一观察结果，我们提出阿尔茨海默病的神经元暴露于低水平但长期的氧化应激，导致神经元引发适应性反应，例如激活应激激活的蛋白激酶途径。
Recent evidence indicates that oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the hallmark pathologies, namely neurofibrillary tangles and senile plaques. The interaction of abnormal mitochondria, redox transition metals, and oxidative stress response elements contributes to the generation of reactive oxygen species in diseased neurons. Oxidative damage to major cellular molecules is seen in a number of disease states that are either acute or chronic and it is apparent that without eliciting compensations that restore redox balance, cells will rapidly succumb to death. Indeed, although oxidative stress is a prominent feature in Alzheimer disease, few vulnerable neurons show clear signs of apoptosis, suggesting that the level of oxidative stress does not significantly exceed neuronal oxidative defenses. In light of this observation, we propose that neurons in Alzheimer disease are exposed to low, but chronic, levels of oxidative stress that lead neurons to elicit adaptive responses such as the activation of stress-activated protein kinase pathways.