Amyloid beta protein-induced neuronal cell death: neurotoxic properties of aggregated amyloid beta protein.
The neurotoxic effects of soluble and aggregated synthetic amyloid beta protein (A beta P) have been investigated in rat primary cultures. Freshly solubilized beta(1-40) was neurotoxic not to immature, but to mature hippocampal neurons. On the other hand, aggregated beta(1-40) was neurotoxic to both. Neurotoxicity induced by aggregated beta(1-40) was 10-fold more potent than soluble beta(1-40) and was not prevented by substance P. The neurotoxicity of aggregated beta(1-40) to cultured neurons depended on the peptide concentration and the duration of exposure to it. Cerebral cortical and hippocampal neurons were significantly susceptible to aggregated beta(1-40) than cerebellar granular cells, and cultured astrocytes were not vulnerable to aggregated beta(1-40) even at high concentrations.
Ueda
K
K
Division of Pharmacology, Shionogi Research Laboratories, Shionogi and Co. Ltd., Toyonaka, Japan.
Fukui
Y
Y
Kageyama
H
H
D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000494:pharmacology / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D013373:Substance P / Q000494:pharmacology; D013778:Tetrazolium Salts; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); D013373:Substance P; C022616:thiazolyl blue