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Preparation of a Well-Defined and Stable β-Barrel Pore-Forming Aβ42 Oligomer

  • Montserrat Serra-Batiste
  • Martí Ninot-Pedrosa
  • Eduard Puig
  • Sonia Ciudad
  • Margarida Gairí
  • Natàlia Carulla
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1779)

Abstract

The formation of amyloid-β peptide (Aβ) oligomers at the cellular membrane is considered a crucial process that underlies neurotoxicity in Alzheimer’s disease (AD). To obtain structural information on this type of oligomers, we were inspired by membrane protein approaches used to stabilize, characterize, and analyze the function of such proteins. Using these approaches, we developed conditions under which Aβ42, the Aβ variant most strongly linked to the aetiology of AD, assembles into an oligomer that inserts into lipid bilayers as a well-defined pore and adopts a specific structure with characteristics of a β-barrel arrangement. We named this oligomer β-barrel Pore-Forming Aβ42 Oligomer (βPFOAβ42). Here, we describe detailed protocols for its preparation and characterization. We expect βPFOAβ42 to be useful in establishing the involvement of membrane-associated Aβ oligomers in AD.

Key words

Alzheimer’s disease Amyloid-β peptide Membrane pore Micelles Oligomer 

Notes

Acknowledgment

M.N.P. and E.P. acknowledge the Spanish Government FPI program for predoctoral fellowships. This work was supported by Program Grants from the MINECO-FEDER (SAF2015-68789), from the Fundació La Marató de TV3 (20140730/31), from the Fondation pour la Researche Médicale (FRM)—Amorçage de Jeunes Equips (AJE20151234751), and from the Counseil Régional d’Aquitaine Limousin Poitou-Charentes (2016-1R30117) to N.C.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Montserrat Serra-Batiste
    • 1
  • Martí Ninot-Pedrosa
    • 1
    • 2
  • Eduard Puig
    • 1
    • 2
  • Sonia Ciudad
    • 1
    • 2
  • Margarida Gairí
    • 3
  • Natàlia Carulla
    • 1
    • 2
  1. 1.Institute for Research in Biomedicine (IRB Barcelona)The Barcelona Institute Science and TechnologyBarcelonaSpain
  2. 2.CBMN (UMR 5248), University of Bordeaux—CNRS—IPB, Institut Européen de Chimie et BiologiePessacFrance
  3. 3.NMR Facility, Scientific and Technological CentersUniversity of Barcelona (CCiTUB)BarcelonaSpain

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