Research Center of Neurology, Russian Academy of Medical Sciences, Moscow, 125367, Russia.
Biochemistry (Mosc). 2014 May;79(5):391-6. doi: 10.1134/S0006297914050022.
Disbalance of zinc (Zn2+) and copper (Cu2+) ions in the central nervous system is involved in the pathogenesis of numerous neurodegenerative disorders such as multisystem atrophy, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Wilson-Konovalov disease, Alzheimer's disease, and Parkinson's disease. Among these, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most frequent age-related neurodegenerative pathologies with disorders in Zn2+ and Cu2+ homeostasis playing a pivotal role in the mechanisms of pathogenesis. In this review we generalized and systematized current literature data concerning this problem. The interactions of Zn2+ and Cu2+ with amyloid precursor protein (APP), β-amyloid (Abeta), tau-protein, metallothioneins, and GSK3β are considered, as well as the role of these interactions in the generation of free radicals in AD and PD. Analysis of the literature suggests that the main factors of AD and PD pathogenesis (oxidative stress, structural disorders and aggregation of proteins, mitochondrial dysfunction, energy deficiency) that initiate a cascade of events resulting finally in the dysfunction of neuronal networks are mediated by the disbalance of Zn2+ and Cu2+.
中枢神经系统中锌（Zn2+）和铜（Cu2+）离子的失衡与多种神经退行性疾病的发病机制有关，如多系统萎缩、肌萎缩侧索硬化症、克雅氏病、威尔逊氏病、阿尔茨海默病和帕金森病。其中，阿尔茨海默病（AD）和帕金森病（PD）是最常见的与年龄相关的神经退行性病变，Zn2+和 Cu2+稳态的紊乱在发病机制中起着关键作用。在这篇综述中，我们总结和系统化了有关这个问题的现有文献数据。考虑了 Zn2+和 Cu2+与淀粉样前体蛋白（APP）、β-淀粉样蛋白（Abeta）、tau 蛋白、金属硫蛋白和 GSK3β 的相互作用，以及这些相互作用在 AD 和 PD 中自由基生成中的作用。对文献的分析表明，AD 和 PD 发病机制的主要因素（氧化应激、蛋白质结构紊乱和聚集、线粒体功能障碍、能量缺乏）通过 Zn2+和 Cu2+的失衡介导。
