Strausak D, Mercer J F, Dieter H H, Stremmel W, Multhaup G
Center for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Burwood, Victoria, Australia.
Brain Res Bull. 2001 May 15;55(2):175-85. doi: 10.1016/s0361-9230(01)00454-3.
Copper is an essential element for the activity of a number of physiologically important enzymes. Enzyme-related malfunctions may contribute to severe neurological symptoms and neurological diseases: copper is a component of cytochrome c oxidase, which catalyzes the reduction of oxygen to water, the essential step in cellular respiration. Copper is a cofactor of Cu/Zn-superoxide-dismutase which plays a key role in the cellular response to oxidative stress by scavenging reactive oxygen species. Furthermore, copper is a constituent of dopamine-beta-hydroxylase, a critical enzyme in the catecholamine biosynthetic pathway. A detailed exploration of the biological importance and functional properties of proteins associated with neurological symptoms will have an important impact on understanding disease mechanisms and may accelerate development and testing of new therapeutic approaches. Copper binding proteins play important roles in the establishment and maintenance of metal-ion homeostasis, in deficiency disorders with neurological symptoms (Menkes disease, Wilson disease) and in neurodegenerative diseases (Alzheimer's disease). The Menkes and Wilson proteins have been characterized as copper transporters and the amyloid precursor protein (APP) of Alzheimer's disease has been proposed to work as a Cu(II) and/or Zn(II) transporter. Experimental, clinical and epidemiological observations in neurodegenerative disorders like Alzheimer's disease and in the genetically inherited copper-dependent disorders Menkes and Wilson disease are summarized. This could provide a rationale for a link between severely dysregulated metal-ion homeostasis and the selective neuronal pathology.
铜是多种生理重要酶活性所必需的元素。与酶相关的功能异常可能导致严重的神经症状和神经疾病：铜是细胞色素c氧化酶的组成成分，该酶催化氧气还原为水，这是细胞呼吸的关键步骤。铜是铜/锌超氧化物歧化酶的辅因子，通过清除活性氧在细胞对氧化应激的反应中起关键作用。此外，铜是多巴胺-β-羟化酶的组成成分，该酶是儿茶酚胺生物合成途径中的关键酶。对与神经症状相关蛋白质的生物学重要性和功能特性进行详细探索，将对理解疾病机制产生重要影响，并可能加速新治疗方法的开发和测试。铜结合蛋白在金属离子稳态的建立和维持、伴有神经症状的缺乏症（门克斯病、威尔逊病）以及神经退行性疾病（阿尔茨海默病）中发挥重要作用。门克斯蛋白和威尔逊蛋白已被鉴定为铜转运蛋白，阿尔茨海默病的淀粉样前体蛋白（APP）被认为可作为铜（II）和/或锌（II）转运蛋白发挥作用。总结了在阿尔茨海默病等神经退行性疾病以及遗传性铜依赖性疾病门克斯病和威尔逊病中的实验、临床和流行病学观察结果。这可为严重失调的金属离子稳态与选择性神经元病理学之间的联系提供理论依据。
