Davies Katherine M, Mercer Julian F B, Chen Nicholas, Double Kay L
Neuroscience Research Australia, Sydney, NSW 2031, Australia School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Melbourne, VIC 3125, Australia.
Clin Sci (Lond). 2016 Apr;130(8):565-74. doi: 10.1042/CS20150153.
Copper is a biometal essential for normal brain development and function, thus copper deficiency or excess results in central nervous system disease. Well-characterized disorders of disrupted copper homoeostasis with neuronal degeneration include Menkes disease and Wilson's disease but a large body of evidence also implicates disrupted copper pathways in other neurodegenerative disorders, including Parkinson's disease, Alzheimer's disease, Amyotrophic lateral sclerosis, Huntington's disease and prion diseases. In this short review we critically evaluate the data regarding changes in systemic and brain copper levels in Parkinson's disease, where alterations in brain copper are associated with regional neuronal cell death and disease pathology. We review copper regulating mechanisms in the human brain and the effects of dysfunction within these systems. We then examine the evidence for a role for copper in pathogenic processes in Parkinson's disease and consider reports of diverse copper-modulating strategies in in vitro and in vivo models of this disorder. Copper-modulating therapies are currently advancing through clinical trials for Alzheimer's and Huntington's disease and may also hold promise as disease modifying agents in Parkinson's disease.
铜是一种对正常大脑发育和功能至关重要的生物金属，因此铜缺乏或过量会导致中枢神经系统疾病。已充分明确的伴有神经元变性的铜稳态破坏疾病包括门克斯病和威尔逊病，但大量证据也表明铜代谢途径紊乱与其他神经退行性疾病有关，包括帕金森病、阿尔茨海默病、肌萎缩侧索硬化症、亨廷顿病和朊病毒病。在这篇简短的综述中，我们批判性地评估了有关帕金森病中全身和大脑铜水平变化的数据，其中大脑铜的改变与局部神经元细胞死亡和疾病病理相关。我们回顾了人类大脑中的铜调节机制以及这些系统功能障碍的影响。然后，我们研究了铜在帕金森病致病过程中作用的证据，并考虑了在该疾病的体外和体内模型中各种铜调节策略的报告。铜调节疗法目前正在推进针对阿尔茨海默病和亨廷顿病的临床试验，并且在帕金森病中作为疾病修饰剂也可能具有前景。
