Potentiation of beta-folding of beta-amyloid peptide 25-35 by aluminum salts.
The formation of the beta pleated configuration of the amyloid peptide fragment 25-35 in aqueous solution, has been studied using thioflavin-T fluorescence as an indicator of such folding. Both phosphate and adenosine triphosphate (ATP) enhance the formation of aggregated beta-sheets. This phosphate-induced aggregation is greater in the presence of aluminum sulfate in a dose dependent manner. In the absence of ATP or phosphate, aluminum salts do not promote aggregation. It is proposed that a particulate aluminum phosphate complex may form critical nuclei upon whose surface the amyloid peptide can change its configuration. This capacity for seeding may be a relevant factor in the formation of insoluble proteinaceous materials such as amyloid plaques and neurofibrillary tangles found in Alzheimer's disease.
Department of Community & Environmental Medicine, Center for Occupational and Environmental Health, University of California, Irvine 92697-1820, USA.
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D000534:Alum Compounds / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D010422:Pentanones / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000187:drug effects
D000534:Alum Compounds; D016229:Amyloid beta-Peptides; D009942:Organometallic Compounds; D010422:Pentanones; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C041524:aluminum sulfate; C058508:tris(acetylacetonate) aluminum(III)