[Neuronal cell damage in aceruloplasminemia].

Aceruloplasminemia is a newly recognized autosomal recessive disorder of iron metabolism that causes neurodegeneration of the retina and basal ganglia, as well as diabetes mellitus. The neurological symptoms in affected patients include involuntary movements, ataxia, and dementia reflecting the sites of iron deposition detected by MRI, and the regions of neurodegeneration observed at autopsy. Excess iron functions as a potent catalyst of biologic oxidation. CSF from affected patients revealed a threefold increased iron concentration associated with increased superoxide dismutase activity and lipid peroxidation products. We found that the amount of iron accumulated in various regions of the brain and visceral organs is correlated with the levels of the oxysterols, including 7-hydroxycholesterol, and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. Positron emission tomography done on brains of aceruloplasminemia patients showed cortical glucose hypometabolism. Enzyme activities in the mitochondrial respiratory chain of the cerebral cortices of the patients were reduced to approximate 62% and 71%, respectively, for complexes I and IV. These findings suggest that iron-mediated free radicals contribute to lipid peroxidation and the impairment of mitochondrial energy metabolism in aceruloplasminemia.