Mechanism of amyloid β protein induced neuronal cell death: current concepts and future perspectives

Summary

Amyloid β protein (A β) is a 40 to 43 amino acid peptide which is associated with plaques in the brains of Alzheimer’s patients and is cytotoxic to cultured neurons. A number of antioxidants protect both primary central nervous system (CNS) cultures and clonal cell lines from Aβ toxicity, suggesting that one pathway to Aβ cytotoxicity results in free radical damage. Aβ causes increased levels of H₂O₂ and lipid peroxides to accumulate in cells. The H₂O₂ degrading enzyme catalase protects cells from Aβ toxicity. Clonal cell lines selected for their resistance to Aβ toxicity also become resistant to the cytolytic action of H₂O₂. In addition, Aβ induces NF-kB activity, a transcription factor thought to be regulated by oxidative stress. Finally, Aβ induced H₂O₂ production and Aβ toxicity are blocked by reagents which inhibit flavin oxidases, suggesting that Aβ activates a member of this class of enzymes. These results show that the cytotoxic action of Aβ on neurons results from free radical damage to susceptible cells (Behl et al., 1994b).