title: Membrane destabilization induced by beta-amyloid peptide 29-42: importance of the amino-terminus.
abstract: Increasing evidence implicates interactions between Abeta-peptides and membrane lipids in Alzheimer's disease. To gain insight into the potential role of the free amino group of the N-terminus of Abeta29-42 fragment in these processes, we have investigated the ability of Abeta29-42 unprotected and Abeta29-42 N-protected to interact with negatively-charged liposomes and have calculated the interaction with membrane lipids by conformational analysis. Using vesicles mimicking the composition of neuronal membranes, we show that both peptides have a similar capacity to induce membrane fusion and permeabilization. The fusogenic effect is related to the appearance of non-bilayer structures where isotropic motions occur as shown by 31P and 2H NMR studies. The molecular modeling calculations confirm the experimental observations and suggest that lipid destabilization could be due to the ability of both peptides to adopt metastable positions in the presence of lipids. In conclusion, the presence of a free or protected (acetylated) amino group in the N-terminus of Abeta29-42 is therefore probably not crucial for destabilizing properties of the C-terminal fragment of Abeta peptides.
authors.affiliation: Unité de Pharmacologie Cellulaire et Moléculaire, Université Catholique de Louvain, Avenue E. Mounier 73, Bt 7370, B-1200, Brussels, Belgium. mingeot@facm.ucl.ac.be
authors.forename: Marie Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
authors.forename: Laurence
authors.initials: L
authors.lastname: Lins
authors.forename: Mariam
authors.initials: M
authors.lastname: Bensliman
authors.forename: Françoise
authors.initials: F
authors.lastname: Van Bambeke
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Der Smissen
authors.forename: Jacques
authors.initials: J
authors.lastname: Peuvot
authors.forename: André
authors.initials: A
authors.lastname: Schanck
authors.forename: Robert
authors.initials: R
authors.lastname: Brasseur
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry; D002463:Cell Membrane Permeability / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry*; D008561:Membrane Fusion / Q000187:drug effects; D008958:Models, Molecular; D009474:Neurons / Q000648:ultrastructure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000494:pharmacology*; D013696:Temperature
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D010446:Peptide Fragments