Fiche publication
Date publication
janvier 2011
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard
Tous les auteurs :
Itkin A, Dupres V, Dufrene YF, Bechinger B, Ruysschaert JM, Raussens V
Lien Pubmed
Résumé
Amyloid beta-peptide (Abeta) is directly linked to Alzheimer's disease (AD). In its monomeric form, Abeta 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 Abeta. We compared the aggregation pattern of Abeta(1-40) and that of Abeta(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+), Abeta(1-40) preferentially formed oligomers similar to those formed by Abeta(1-40)E22G with or without added Ca(2+), whereas in the absence of added Ca(2+) the Abeta(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 beta-sheet to the parallel beta-sheet conformation characteristic of fibrils. Overall, these results led us to conclude that calcium ions stimulate the formation of oligomers of Abeta(1-40), that have been implicated in the pathogenesis of AD.
Référence
PLoS One. 2011 Mar 28;6(3):e18250.
