Copper homeostasis in the CNS - A novel link between the NMDA receptor and copper homeostasis in the hippocampus
Copper homeostasis in the CNS - A novel link between the NMDA receptor and copper homeostasis in the hippocampus
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DOI：
10.1385/mn:33:2:81
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发表时间：
2006-04-01
影响因子：
5.1
通讯作者：
Gitlin, JD
中科院分区：
文献类型：
--
作者：
Schlief, ML;Gitlin, JD
铜是一种必需的营养素，在中枢神经系统的生物化学中起着重要作用，如门克斯病患者所证明的，门克斯病是一种致命的儿童神经退行性疾病，由铜转运P型腺苷三磷酸酶（ATP酶）的功能丧失引起。尽管临床和实验数据表明铜在脑功能中的作用，但受铜影响的关键事件的机制和时间仍然知之甚少。已确定Menkes ATP酶在海马神经元中N-甲基-D-天冬氨酸（NMDA）受体依赖性可释放铜库的可用性中的新作用，表明中枢神经系统内连接铜稳态和神经元激活的独特机制。本文探讨了铜作为神经元传递的调节剂的证据，以及从神经元释放内源性铜可能调节NMDA受体活性。铜稳态受损与神经病理生理学之间的关系表明，铜外排障碍可能会改变神经元功能，从而导致快速神经元变性。
Copper is an essential nutrient that plays a fundamental role in the biochemistry of the central nervous system, as evidenced by patients with Menkes disease, a fatal neurodegenerative disorder of childhood resulting from the loss-of-function of a copper-transporting P-type adenosine triphosphatase (ATPase). Despite clinical and experimental data indicating a role for copper in brain function, the mechanisms and timing of the critical events affected by copper remain poorly understood. A novel role for the Menkes ATPase has been identified in the availability of an N-methyl-D-aspartate (NMDA) receptor-dependent, releasable pool of copper in hippocampal neurons, suggesting a unique mechanism linking copper homeostasis and neuronal activation within the central nervous system. This article explores the evidence that copper acts as a modulator of neuronal transmission, and that the release of endogenous copper from neurons may regulate NMDA receptor activity. The relationship between impaired copper homeostasis and neuropathophysiology suggests that impairment of copper efflux could alter neuronal function and thus contribute to rapid neuronal degeneration.