Zhu Xiongwei, Raina Arun K, Lee Hyoung-Gon, Chao Mark, Nunomura Akihiko, Tabaton Massimo, Petersen Robert B, Perry George, Smith Mark A
Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Antioxid Redox Signal. 2003 Oct;5(5):571-6. doi: 10.1089/152308603770310220.
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.
最近的证据表明，氧化应激在阿尔茨海默病进展的早期就会出现，远早于标志性病理特征即神经原纤维缠结和老年斑的形成。异常线粒体、氧化还原过渡金属和氧化应激反应元件之间的相互作用促使患病神经元中活性氧的产生。在许多急性或慢性疾病状态下均可观察到主要细胞分子的氧化损伤，显然，如果不引发恢复氧化还原平衡的代偿机制，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显著特征，但很少有易损神经元表现出明显的凋亡迹象，这表明氧化应激水平并未显著超过神经元的氧化防御能力。鉴于这一观察结果，我们提出，阿尔茨海默病中的神经元暴露于低水平但持续的氧化应激中，这会导致神经元引发适应性反应，如应激激活蛋白激酶途径的激活。
