Copper deficiency.
OBJECTIVE
Reports of the neurologic findings in adults with acquired copper deficiency as well as the development of novel models for Menkes disease have permitted a greater understanding of the role of copper in the central nervous system. A role of mitochondrial copper homeostasis in cellular energy metabolism suggests roles for this metal in cellular differentiation and biochemical adaptation.


RESULTS
Acquired copper deficiency in adults is reported with increasing frequency, often without any identifiable cause. Chemical genetic studies identified a zebrafish model of Menkes disease that can be used for high-throughput therapeutics and revealed a hierarchy of copper distribution during development. Studies in mice reveal that the copper transport protein Ctr1 is essential for intestinal copper absorption and suggest a unique role for copper in axonal extension, excitotoxic cell death and synaptic plasticity in the central nervous system. Lastly, recent biochemical studies indicate a central role for the mitochondrial matrix in cellular copper metabolism.


CONCLUSIONS
The recent developments in our understanding of copper deficiency and copper homeostasis outlined in this review provide an exciting platform for future investigations intended to elucidate the role of copper in central nervous system development and disease.
Madsen
Erik
E
Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
Gitlin
Jonathan D
JD
D000818:Animals; D001692:Biological Transport / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D027682:Cation Transport Proteins / Q000235:genetics; D002493:Central Nervous System Diseases / Q000209:etiology* / Q000235:genetics; D003300:Copper / Q000032:analysis / Q000172:deficiency* / Q000378:metabolism; D000079923:Copper Transporter 1; D004195:Disease Models, Animal; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000209:etiology* / Q000235:genetics; D051379:Mice; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000502:physiology; D018832:Molecular Chaperones
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C400285:SCO2 protein, human; D003300:Copper