Greenough M A, Ramírez Munoz A, Bush A I, Opazo C M
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Metallomics. 2016 Sep 1;8(9):831-9. doi: 10.1039/c6mt00095a. Epub 2016 Jul 11.
Copper is an essential metal ion that provides catalytic function to numerous enzymes and also regulates neurotransmission and intracellular signaling. Conversely, a deficiency or excess of copper can cause chronic disease in humans. Menkes and Wilson disease are two rare heritable disorders of copper transport that are characterized by copper deficiency and copper overload, respectively. Changes to copper status are also a common feature of several neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS). In the case of AD, which is characterized by brain copper depletion, changes in the distribution of copper has been linked with various aspects of the disease process; protein aggregation, defective protein degradation, oxidative stress, inflammation and mitochondrial dysfunction. Although AD is a multifactorial disease that is likely caused by a breakdown in multiple cellular pathways, copper and other metal ions such as iron and zinc play a central role in many of these cellular processes. Pioneering work by researchers who have studied relatively rare copper transport diseases has shed light on potential metal ion related disease mechanisms in other forms of neurodegeneration such as AD.
铜是一种必需的金属离子，它为众多酶提供催化功能，还能调节神经传递和细胞内信号传导。相反，铜缺乏或过量会导致人类患慢性病。门克斯病和威尔逊病是两种罕见的铜转运遗传性疾病，分别以铜缺乏和铜过载为特征。铜状态的变化也是包括阿尔茨海默病（AD）、帕金森病（PD）和肌萎缩侧索硬化症（ALS）在内的几种神经退行性疾病的共同特征。就以脑铜耗竭为特征的AD而言，铜分布的变化与疾病过程的各个方面有关；蛋白质聚集、蛋白质降解缺陷、氧化应激、炎症和线粒体功能障碍。尽管AD是一种多因素疾病，可能由多种细胞途径的破坏引起，但铜以及其他金属离子如铁和锌在许多这些细胞过程中起着核心作用。研究相对罕见的铜转运疾病的研究人员的开创性工作揭示了其他形式神经退行性疾病如AD中潜在的金属离子相关疾病机制。
