Mechanism of amyloid beta protein induced neuronal cell death: current concepts and future perspectives.
Amyloid beta protein (A beta) 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 A beta toxicity, suggesting that one pathway to A beta cytotoxicity results in free radical damage. A beta causes increased levels of H2O2 and lipid peroxides to accumulate in cells. The H2O2 degrading enzyme catalase protects cells from A beta toxicity. Clonal cell lines selected for their resistance to A beta toxicity also become resistant to the cytolytic action of H2O2. In addition, A beta induces NF-kB activity, a transcription factor thought to be regulated by oxidative stress. Finally, A beta induced H2O2 production and A beta toxicity are blocked by reagents which inhibit flavin oxidases, suggesting that A beta activates a member of this class of enzymes. These results show that the cytotoxic action of A beta on neurons results from free radical damage to susceptible cells (Behl et al., 1994b).
Behl
C
C
Clinical Institute, Max-Planck-Institute of Psychiatry, Munich, Federal Republic of Germany.
Sagara
Y
Y
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000032:analysis / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000473:pathology / Q000502:physiology / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D015227:Lipid Peroxidation; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D009498:Neurotoxins; D018384:Oxidative Stress
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D016328:NF-kappa B; D009498:Neurotoxins