Effects of aluminum on the neurotoxicity of primary cultured neurons and on the aggregation of beta-amyloid protein.
Recent epidemiological, neuropathological, and biochemical studies have suggested a possible link between the neurotoxicity of aluminum and the pathogenesis of Alzheimer's disease. However, this relationship remains controversial. To investigate detailed characteristics of neurotoxicity of aluminum, we used primary cultured neurons of rat cerebral cortex as an in vitro model system for the observation of morphological changes induced by chronic exposure to aluminum. Although the exposure to aluminum chloride (10-100 microM) for 1 week did not cause marked neuronal death, degeneration of neuritic processes and accumulation of tau protein and beta-amyloid protein appeared after chronic exposure to 50 microM aluminum chloride for more than 3 weeks. We also investigated the polymerization of beta-amyloid protein in vitro using the immunoblotting technique. We thus found that aluminum induced conformational changes in beta-amyloid protein and enhanced its aggregation in vitro. The aggregated beta-amyloid protein was dissolved by the addition of desferrioxamine, a chelator of aluminum. The aggregated beta-amyloid protein pre-incubated with aluminum formed fibrillar deposits on the surface of cultured neurons.
Kawahara
M
M
Department of Molecular and Cellular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan. kawamasa@tmin.ac.jp
Kato
M
M
Kuroda
Y
Y
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000633:toxicity*; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001252:Astringents / Q000633:toxicity; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002712:Chlorides / Q000633:toxicity; D004781:Environmental Exposure / Q000009:adverse effects; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D016900:Neurofilament Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D016875:tau Proteins / Q000187:drug effects / Q000378:metabolism
D017607:Aluminum Compounds; D016229:Amyloid beta-Peptides; D001252:Astringents; D002712:Chlorides; D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D009498:Neurotoxins; D010446:Peptide Fragments; D016875:tau Proteins; D000077410:Aluminum Chloride