Perry G, Smith M A
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Neurologia. 1999 Feb;14(2):78-84.
The two most striking features of Alzheimer's disease are: a) the multitude of abnormalities affecting essentially every system, and b) the strict age dependence. Recent work suggests that both features are linked to increased oxidative stress that damages lipids, proteins and nucleic acids and results in redox-active metal accumulations, mitochondrial damage and formation of advanced glycation endproducts. Interestingly, beta-protein precursor, amyloid-beta, presenilins and apolipoprotein E have all been linked to reactive oxygen species production or with apoptosis, a process intimately associated with oxidative stress. In therapeutics, the commonality between a number of efficacious agents appears to be oxidative stress reduction. Therefore, we contend that oxidative stress is the element that links the multitude of changes in Alzheimer's disease and that a reduction of oxidative stress will have a dramatic effect on reducing the incidence or progression of Alzheimer's disease.
a）几乎影响每个系统的众多异常情况；b）严格的年龄依赖性。最近的研究表明，这两个特征都与氧化应激增加有关，氧化应激会损害脂质、蛋白质和核酸，并导致具有氧化还原活性的金属积累、线粒体损伤以及晚期糖基化终产物的形成。有趣的是，β-蛋白前体、β-淀粉样蛋白、早老素和载脂蛋白E都与活性氧的产生或细胞凋亡有关，而细胞凋亡是一个与氧化应激密切相关的过程。在治疗方面，许多有效药物之间的共性似乎是降低氧化应激。因此，我们认为氧化应激是将阿尔茨海默病中众多变化联系起来的因素，降低氧化应激将对降低阿尔茨海默病的发病率或进展产生显著影响。
