Oxidative Mechanisms in β-Amyloid Cytotoxicity

Amyloid β-peptide has been demonstrated to be toxic for primary and clonal neuronal cell linesin vitro. Oxidative mechanisms have been implicated in this pathway at several points, including the aggregation of β-amyloid necessary for cytotoxic activity, generation of radicals by the peptide itself, and intracellularly in response to toxic β-amyloid peptides. Supporting an oxidative hypothesis are the observations that cells mount a stress response to β-amyloid similar to that seen in response to oxidative stress and that they may be rescued from cytotoxicity by antioxidants, inhibitors of oxidative enzyme metabolism, and overexpression of antioxidant enzymes. Although the source(s) of the oxygen radicals has not yet been identified, altered antioxidant enzyme levels and oxidative by-products in Alzheimer's disease brain samples relate thein vitrostudies to the human disease.