Molecular Neurobiology

, Volume 33, Issue 2, pp 81–90

Copper homeostasis in the CNS

A novel link between the NMDA receptor and copper homeostasis in the hippocampus


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.

Index Entries

Copper NMDA receptor CNS hippocampus P-type ATPase Menkes disease 


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Copyright information

© Humana Press Inc 2006

Authors and Affiliations

  1. 1.Edward Mallickrodt Department of PediatricsWashington University School of MedicineSt. Louis

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