Locatelli Martina, Farina Cinthia
Institute of Experimental Neurology, Division of Neuroscience, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Neural Regen Res. 2025 Apr 1;20(4):1058-1068. doi: 10.4103/NRR.NRR-D-24-00110. Epub 2024 May 17.
Copper is a transition metal and an essential element for the organism, as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs, including the central nervous system. Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B, Menkes disease and Wilson's disease, respectively, and also in multifactorial neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology, reports about unbalances in copper levels and/or distribution under disease, describes relevant animal models for human disorders where copper metabolism genes are dysregulated, and discusses relevant therapeutic approaches modulating copper availability. Overall, alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
铜是一种过渡金属，也是生物体必需的元素，因为其体内稳态的改变导致金属积累或缺乏会在包括中枢神经系统在内的多个器官产生病理影响。中枢铜调节异常已在两种分别以铜转运ATP酶ATP7A和ATP7B突变特征的遗传性疾病（门克斯病和威尔逊病）中得到证实，也在诸如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和多发性硬化症等多因素神经疾病中得到证实。本综述总结了目前关于铜在中枢神经系统生理和病理中的作用的知识，报道了疾病状态下铜水平和/或分布的失衡情况，描述了铜代谢基因失调的人类疾病相关动物模型，并讨论了调节铜可利用性的相关治疗方法。总体而言，铜代谢的改变可能有助于中枢神经系统疾病的病因形成，并代表恢复组织稳态的相关治疗靶点。
