[Neurodegeneration Associated with Metal Metabolism]

Neurodegeneration with brain iron accumulation (NBIA) comprises a heterogeneous group of inherited neurodegenerative disorders collectively characterized by extrapyramidal movement disorders and abnormal iron accumulation in the nuclei of the deep basal ganglia of the brain. Ten NBIA genes have been identified. Aceruloplasminemia is a type of NBIA associated with copper metabolism. Ceruloplasmin contains 95% of the copper in human serum and plays an important role in iron efflux from mammalian cells. The relationship between ceruloplasmin and neurodegenerative diseases was revealed by a decrease in the serum ceruloplasmin concentration, which is characteristic of hepatolenticular degeneration with copper overload, in patients with Wilson's disease. Serum ceruloplasmin levels are typically decreased in patients with Wilson's disease, Menkes's disease (copper deficiency), and aceruloplasminemia. The molecular pathogenesis underlying different forms of neurodegeneration has provided new insights into the pathways of brain iron and copper metabolism.