title: The role of copper in neurodegenerative disease.
abstract: Copper is an essential trace metal which plays a fundamental role in the biochemistry of the human nervous system. Menkes disease and Wilson disease are inherited disorders of copper metabolism and the dramatic neurodegenerative phenotypes of these two diseases underscore the essential nature of copper in nervous system development as well as the toxicity of this metal when neuronal copper homeostasis is perturbed. Ceruloplasmin contains 95% of the copper found in human plasma and inherited loss of this essential ferroxidase is associated with progressive neurodegeneration of the retina and basal ganglia. Gain-of-function mutations in the cytosolic copper enzyme superoxide dismutase result in the motor neuron degeneration of amyotrophic lateral sclerosis and current evidence suggests a direct pathogenic role for copper in this process. Recent studies have also implicated copper in the pathogenesis of neuronal injury in Alzheimer's disease and the prion-mediated encephalopathies, suggesting that further elucidation of the mechanisms of copper trafficking and metabolism within the nervous system will be of direct relevance to our understanding of the pathophysiology and treatment of neurodegenerative disease.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Waggoner
authors.forename: T B
authors.initials: TB
authors.lastname: Bartnikas
authors.forename: J D
authors.initials: JD
authors.lastname: Gitlin
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism / Q000502:physiology; D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000502:physiology; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D027682:Cation Transport Proteins; D002570:Ceruloplasmin / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D003300:Copper / Q000378:metabolism* / Q000502:physiology*; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007706:Menkes Kinky Hair Syndrome / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D019636:Neurodegenerative Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D017096:Prion Diseases / Q000378:metabolism / Q000473:pathology; D011328:Prions / Q000378:metabolism / Q000502:physiology; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid
chemical_list: D016229:Amyloid beta-Peptides; C486201:Atp7a protein, mouse; D002352:Carrier Proteins; D027682:Cation Transport Proteins; D011328:Prions; D011993:Recombinant Fusion Proteins; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases