Department of Physiology, Johns Hopkins Medical Institutes, 725 N Wolfe St, Baltimore, MD, 21205, USA.
Department of Molecular and Medical Genetics, Oregon Health and Sciences University, Portland, OR, 97329, USA.
J Biol Inorg Chem. 2019 Dec;24(8):1179-1188. doi: 10.1007/s00775-019-01737-3. Epub 2019 Nov 5.
Copper (Cu) plays an essential role in the development and function of the brain. In humans, genetic disorders of Cu metabolism may cause either severe Cu deficiency (Menkes disease) or excessive Cu accumulation (Wilson disease) in the brain tissue. In either case, the loss of Cu homeostasis results in catecholamine misbalance, abnormal myelination of neurons, loss of normal brain architecture, and a spectrum of neurologic and/or psychiatric manifestations. Several metabolic processes have been identified as particularly sensitive to Cu dis-homeostasis. This review focuses on the role of Cu in noradrenergic neurons and summarizes the current knowledge of mechanisms that maintain Cu homeostasis in these cells. The impact of Cu misbalance on catecholamine metabolism and functioning of noradrenergic system is discussed.
铜(Cu)在大脑的发育和功能中起着至关重要的作用。在人类中,Cu 代谢的遗传疾病可能导致脑组织中 Cu 严重缺乏(Menkes 病)或过度积累(Wilson 病)。在这两种情况下,Cu 动态平衡的丧失都会导致儿茶酚胺失衡、神经元髓鞘异常、正常脑结构丧失以及一系列神经和/或精神表现。已经确定了几种代谢过程对 Cu 动态平衡失调特别敏感。本综述重点介绍了 Cu 在去甲肾上腺素能神经元中的作用,并总结了目前关于维持这些细胞中 Cu 动态平衡的机制的知识。讨论了 Cu 失衡对儿茶酚胺代谢和去甲肾上腺素能系统功能的影响。