Calcium Ions Promote Formation of Amyloid beta-Peptide (1-40) Oligomers Causally Implicated in Neuronal Toxicity of Alzheimer's Disease
| Autor: | Anna Itkin, Vincent Raussens, Vincent Dupres, Jean Marie Ruysschaert, Burkhard Bechinger, Yves F. Dufrêne |
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| Přispěvatelé: | Université libre de Bruxelles, Brussels - Laboratory of structure and function of biological membranes, UCL - SST/IMCN/BSMA - Bio and soft matter, Université de Strasbourg, France - International Center for Frontier Research in Chemistry, Chemistry Institute, Membrane Biophysics and NMR |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Peptide
Biochemistry Protein Structure Secondary chemistry.chemical_compound Spectroscopy Fourier Transform Infrared Amyloid beta-Peptides -- chemistry -- toxicity chemistry.chemical_classification Neurons Multidisciplinary P3 peptide Monomer Neurology Medicine Thioflavin Alzheimer's disease Biologie Research Article Protein Structure Neurons -- drug effects -- pathology Amyloid Science Alzheimer Disease -- pathology Blotting Western chemistry.chemical_element Calcium Fibril Models Biological Fluorescence Alzheimer Disease medicine Thiazoles -- metabolism Humans Benzothiazoles Protein Interactions Protein Structure Quaternary Biology Ions Amyloid beta-Peptides Proteins Médecine pathologie humaine medicine.disease Sciences biomédicales Ingénierie biomédicale Thiazoles chemistry Mutant Proteins -- chemistry -- toxicity Mutant Proteins Dementia Calcium -- pharmacology |
| Zdroj: | PLoS One, Vol. 6, no. 3, p. e18250 (2011) PloS one, 6 (3 PLoS ONE PLoS ONE, Vol 6, Iss 3, p e18250 (2011) |
| Popis: | Amyloid β-peptide (Aβ) is directly linked to Alzheimer's disease (AD). In its monomeric form, Aβ aggregates to produce fibrils and a range of oligomers, the latter being the most neurotoxic. Dysregulation of Ca(2+) homeostasis in aging brains and in neurodegenerative disorders plays a crucial role in numerous processes and contributes to cell dysfunction and death. Here we postulated that calcium may enable or accelerate the aggregation of Aβ. We compared the aggregation pattern of Aβ(1-40) and that of Aβ(1-40)E22G, an amyloid peptide carrying the Arctic mutation that causes early onset of the disease. We found that in the presence of Ca(2+), Aβ(1-40) preferentially formed oligomers similar to those formed by Aβ(1-40)E22G with or without added Ca(2+), whereas in the absence of added Ca(2+) the Aβ(1-40) aggregated to form fibrils. Morphological similarities of the oligomers were confirmed by contact mode atomic force microscopy imaging. The distribution of oligomeric and fibrillar species in different samples was detected by gel electrophoresis and Western blot analysis, the results of which were further supported by thioflavin T fluorescence experiments. In the samples without Ca(2+), Fourier transform infrared spectroscopy revealed conversion of oligomers from an anti-parallel β-sheet to the parallel β-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Aβ(1-40), that have been implicated in the pathogenesis of AD. Journal Article Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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