Alzheimer's disease amyloid beta peptide 25-35 inhibits lipid peroxidation as a result of its membrane interactions.
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.
Walter
M F
MF
Laboratory for Membrane Structure Studies, MCP-Hahnemann School of Medicine, Allegheny University of the Health Sciences, Pittsburgh, Pennsylvania 15212-4772, USA.
Mason
P E
PE
Mason
R P
RP
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
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