Aggregation of amyloid beta-protein and its neurotoxicity: enhancement by aluminum and other metals.
The aggregation of amyloid beta-protein has been suggested to enhance its neurotoxicity in cultured hippocampal neurons. We found that aluminum, an epidemiologic risk factor for Alzheimer's disease, promoted the aggregation of synthetic amyloid beta-protein (beta 1-40) using immunoblotting and centrifugation. There were no significant changes by Ca or Mg. Other metals including Zn, Fe caused the small degree of aggregation compared to Al. Furthermore, beta 1-40 which was aggregated by aluminum was applied on cultured rat hippocampal neurons, and the characteristic deposition of amyloid fibrils was observed on cultured neurons. These results suggested that the degeneration of neurons and the deposition of amyloid beta-protein were enhanced by aluminum.
Kuroda
Y
Y
Department of Molecular & Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience.
Kawahara
M
M
D000535:Aluminum / Q000494:pharmacology / Q000633:toxicity*; D000544:Alzheimer Disease / Q000209:etiology*; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D001704:Biopolymers / Q000737:chemistry; D002118:Calcium / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured; D004357:Drug Synergism; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008959:Models, Neurological; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011228:Prealbumin / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats
D016229:Amyloid beta-Peptides; D001704:Biopolymers; D010446:Peptide Fragments; D011228:Prealbumin; C078592:amyloid beta-protein (1-40); D000535:Aluminum; D008274:Magnesium; D002118:Calcium