Department of Parasitology, Faculty of Science, Charles University, Prague, Czech Republic.
Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Burwood Campus, 221 Burwood Highway, Burwood, Victoria 3125, Australia.
Prog Neurobiol. 2014 May;116:33-57. doi: 10.1016/j.pneurobio.2014.01.002. Epub 2014 Jan 17.
Copper is an important trace element that is required for essential enzymes. However, due to its redox activity, copper can also lead to the generation of toxic reactive oxygen species. Therefore, cellular uptake, storage as well as export of copper have to be tightly regulated in order to guarantee sufficient copper supply for the synthesis of copper-containing enzymes but also to prevent copper-induced oxidative stress. In brain, copper is of importance for normal development. In addition, both copper deficiency as well as excess of copper can seriously affect brain functions. Therefore, this organ possesses ample mechanisms to regulate its copper metabolism. In brain, astrocytes are considered as important regulators of copper homeostasis. Impairments of homeostatic mechanisms in brain copper metabolism have been associated with neurodegeneration in human disorders such as Menkes disease, Wilson's disease and Alzheimer's disease. This review article will summarize the biological functions of copper in the brain and will describe the current knowledge on the mechanisms involved in copper transport, storage and export of brain cells. The role of copper in diseases that have been connected with disturbances in brain copper homeostasis will also be discussed.
铜是一种重要的微量元素，是必需酶的组成部分。然而，由于其氧化还原活性，铜也会导致有毒的活性氧物质的产生。因此，细胞摄取、储存和铜的输出必须受到严格的调节，以保证合成含铜酶所需的足够的铜供应，同时防止铜诱导的氧化应激。在大脑中，铜对正常发育很重要。此外，铜缺乏和铜过量都会严重影响大脑功能。因此，这个器官拥有充足的机制来调节其铜代谢。在大脑中，星形胶质细胞被认为是铜动态平衡的重要调节者。脑铜代谢稳态机制的损伤与 Menkes 病、Wilson 病和阿尔茨海默病等人类疾病的神经退行性变有关。本文综述了铜在大脑中的生物学功能，并描述了目前关于铜在脑细胞中运输、储存和输出的机制的认识。还讨论了铜在与脑铜动态平衡紊乱有关的疾病中的作用。
