Multhaup G, Ruppert T, Schlicksupp A, Hesse L, Beher D, Masters C L, Beyreuther K
ZMBH-Center for Molecular Biology Heidelberg, University of Heidelberg, Germany.
Biochem Pharmacol. 1997 Sep 1;54(5):533-9. doi: 10.1016/s0006-2952(97)00062-2.
Although a consensus that Alzheimer's disease (AD) is a single disease has not been reached yet, the involvement of the amyloid precursor protein (APP) and betaA4 (A beta) in the pathologic changes advances our understanding of the underlying molecular alterations. Increasing evidence implicates oxidative stress in the neurodegenerative process of AD. This hypothesis is based on the toxicity of betaA4 in cell cultures, and the findings that aggregation of betaA4 can be induced by metal-catalyzed oxidation and that free oxygen radicals may be involved in APP metabolism. Another neurological disorder, familial amyotrophic lateral sclerosis (FALS), supports our view that AD and FALS may be linked through a common mechanism. In FALS, SOD-Cu(I) complexes are affected by hydrogen peroxide and free radicals are produced. In AD, the reduction of Cu(II) to Cu(I) by APP involves an electron-transfer reaction and could also lead to a production of hydroxyl radicals. Thus, copper-mediated toxicity of APP-Cu(II)/(I) complexes may contribute to neurodegeneration in AD.
尽管尚未就阿尔茨海默病（AD）是一种单一疾病达成共识，但淀粉样前体蛋白（APP）和βA4（Aβ）参与病理变化这一情况推进了我们对潜在分子改变的理解。越来越多的证据表明氧化应激参与了AD的神经退行性过程。这一假说基于βA4在细胞培养中的毒性，以及βA4聚集可由金属催化氧化诱导且游离氧自由基可能参与APP代谢的发现。另一种神经疾病，家族性肌萎缩侧索硬化症（FALS），支持了我们认为AD和FALS可能通过共同机制相联系的观点。在FALS中，超氧化物歧化酶-铜（I）复合物受过氧化氢影响并产生自由基。在AD中，APP将铜（II）还原为铜（I）涉及一个电子转移反应，也可能导致羟基自由基的产生。因此，铜介导的APP-铜（II）/（I）复合物毒性可能促成了AD中的神经退行性变。
