title: Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions.
abstract: The biological activity of the Alzheimer's disease amyloid beta protein may be related to modulation of membrane lipid peroxidation. The effect of amyloid beta protein fragment 25-35 [A beta(25-35)] on lipid peroxidation was examined in liposomes enriched with polyunsaturated fatty acids. The activity of A beta(25-35) was compared to that of A beta(25-35) with either a scrambled sequence [A beta(25-35)scram] or a peptide sequence in which methionine was replaced with leucine [A beta(25-35) met]. A beta(25-35) inhibited lipid peroxidation in a dose- and time-dependent manner. The antioxidant activity of A beta(25-35) was observed at concentrations as low as 10 nM. The relative antioxidant activities of the amyloid beta protein fragments were as follows: A beta(25-35) > A beta(25-35) met > A beta(25-35)scram. The two more potent peptides intercalated into the membrane hydrocarbon core, as determined by small-angle x-ray diffraction approaches. These findings indicate that the amphiphilic A beta(25-35) peptide inhibits lipid peroxidation at low concentrations as a result of physicochemical interactions with the membrane lipid bilayer.
authors.affiliation: Laboratory for Membrane Structure Studies, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212-4772, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Walter
authors.forename: P E
authors.initials: PE
authors.lastname: Mason
authors.forename: R P
authors.initials: RP
authors.lastname: Mason
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008563:Membrane Lipids / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010446:Peptide Fragments; D010713:Phosphatidylcholines; C074636:amyloid beta-protein (25-35); C015153:1,2-dilauroylphosphatidylcholine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine