Stabilization of neurotoxic soluble beta-sheet-rich conformations of the Alzheimer's disease amyloid-beta peptide.

TEW, Deborah J, BOTTOMLEY, Stephen P, SMITH, David P, CICCOTOSTO, Giuseppe D, BABON, Jeffrey, HINDS, Mark G, MASTERS, Colin L, CAPPAI, Roberto and BARNHAM, Kevin J (2008). Stabilization of neurotoxic soluble beta-sheet-rich conformations of the Alzheimer's disease amyloid-beta peptide. Biophysical journal, 94 (7), 2752-2766.

Full text not available from this repository.
Link to published version:: https://doi.org/10.1529/biophysj.107.119909
Related URLs:

    Abstract

    An emerging paradigm for degenerative diseases associated with protein misfolding, such as Alzheimer's disease, is the formation of a toxic species due to structural transitions accompanied by oligomerization. Increasingly, the focus in Alzheimer's disease is on soluble oligomeric forms of the amyloid-beta peptide (Abeta) as the potential toxic species. Using a variety of methods, we have analyzed how sodium dodecyl sulphate (SDS) modulates the folding of Abeta40 and 42 and found that submicellar concentrations of SDS solubilize Abeta and induce structural transitions. Under these conditions, Abeta40 and 42 are interconverting oligomeric ensembles with a predominantly beta-sheet structure. The Abeta42 soluble oligomers form beta-sheet structures more readily and have increased stability compared with Abeta40 under identical conditions. The presence of added Cu(2+) significantly promotes and stabilizes the formation of the soluble oligomeric beta-sheet structures but these structures are nonamyloidogenic. In contrast, in the absence of added Cu(2+), these beta-sheet oligomers possess the hallmarks of amyloidogenic structures. These SDS-induced beta-sheet forms of Abeta, both in the presence and absence of Cu(2+), are toxic to neuronal cells.

    Item Type: Article
    Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomolecular Sciences Research Centre
    Identification Number: https://doi.org/10.1529/biophysj.107.119909
    Page Range: 2752-2766
    Depositing User: Jamie Young
    Date Deposited: 03 Jun 2015 10:41
    Last Modified: 13 Jun 2017 13:29
    URI: http://shura.shu.ac.uk/id/eprint/9994

    Actions (login required)

    View Item View Item

    Downloads

    Downloads per month over past year

    View more statistics