ABSTRACT
This chapter discusses the metal binding and radical generation of proteins in human neurological diseases and aging. Organisms take great care in the handling of the transition metals iron and copper that can undergo oxidation-reduction reactions. Oxidative stress, a condition describing the production of oxygen radicals beyond a threshold for proper antioxidant neutralization, has been implicated in the pathogenesis of several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease (AD), and Huntington's disease, and in chronic manganese-induced neurotoxicity. The most convincing link so far between neurological disorders and oxygen radical formation is the strong association observed between familial amyotrophic lateral sclerosis and mutations in the copper/zinc- superoxide dismutase gene. Of particular importance to AD is the binding of metal ions that are potentially neurotoxic. The amyloid precursor protein interacts specifically with zinc and copper at two distinct sites in the ectodomain.
