The role of copper in neurodegenerative disease

Copper is an essential trace metal which plays a fundamental role in the bi ochemistry of the human nervous system. Menkes disease and Wilson disease a re inherited disorders of copper metabolism and the dramatic neurodegenerat ive phenotypes of these two diseases underscore the essential nature of cop per in nervous system development as well as the toxicity of this metal whe n neuronal copper homeostasis is perturbed. Ceruloplasmin contains 95% of t he copper found in human plasma and inherited loss of this essential ferrox idase is associated with progressive neurodegeneration of the retina and ba sal ganglia. Gain-of-function mutations in the cytosolic copper enzyme supe roxide dismutase result in the motor neuron degeneration of amyotrophic lat eral sclerosis and current evidence suggests a direct pathogenic role for c opper in this process. Recent studies have also implicated copper in the pa thogenesis 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 he of dir ect relevance to our understanding of the pathophysiology and treatment of neurodegenerative disease. (C) 1999 Academic Press.