title: The iAβ5p β-breaker peptide regulates the Aβ(25-35) interaction with lipid bilayers through a cholesterol-mediated mechanism.
abstract: Alzheimer's disease is characterized by the deposition of aggregates of the β-amyloid peptide (Aβ) in the brain. A potential therapeutic strategy for Alzheimer's disease is the use of synthetic β-sheet breaker peptides, which are capable of binding Aβ but unable to become part of a β-sheet structure, thus inhibiting the peptide aggregation. Many studies suggest that membranes play a key role in the Aβ aggregation; consequently, it is strategic to investigate the interplay between β-sheet breaker peptides and Aβ in the presence of lipid bilayers. In this work, we focused on the effect of the β-sheet breaker peptide acetyl-LPFFD-amide, iAβ5p, on the interaction of the Aβ(25-35) fragment with lipid membranes, studied by Electron Spin Resonance spectroscopy, using spin-labeled membrane components (either phospholipids or cholesterol). The ESR results show that iAβ5p influences the Aβ(25-35) interaction with the bilayer through a cholesterol-mediated mechanism: iAβ5p withholds cholesterol in the inner hydrophobic core of the bilayer, making the interfacial region more fluid and capable to accommodate Aβ(25-35). As a consequence, iAβ5p prevents the Aβ(25-35) release from the lipid membrane, which is the first step of the β-amyloid aggregation process.
authors.affiliation: Department of Chemistry, University of Naples Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vitiello
authors.forename: Manuela
authors.initials: M
authors.lastname: Grimaldi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: D'Ursi
authors.forename: Gerardino
authors.initials: G
authors.lastname: D'Errico
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000627:therapeutic use; D002784:Cholesterol / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C474023:iAbeta5 peptide; D002784:Cholesterol