Effect of trehalose on amyloid beta (29-40)-membrane interaction.
A growing body of experimental evidence indicates that the interaction between amyloid beta peptide and lipid bilayer membranes plays an important role in the development of Alzheimer disease. Recent experimental evidence also suggests that trehalose, a simple disaccharide, reduces the toxicity of amyloid beta peptide. Molecular simulations are used to examine the effect of trehalose on the conformational stability of amyloid beta peptide in aqueous solution and its effect on the interaction between amyloid beta peptide and a model phospholipid bilayer membrane. It is found that, in aqueous solution, the peptide exhibits a random coil conformation but, in the presence of trehalose, it adopts an alpha helical conformation. It is then shown that the insertion of amyloid beta peptide into a membrane is more favorable when the peptide is folded into an alpha-helix than in a random coil conformation, thereby suggesting that trehalose promotes the insertion of alpha-helical amyloid beta into biological membranes.
Reddy
Allam S
AS
Department of Chemical Engineering, University of Wisconsin, Madison, Wisconsin 53706-1691, USA.
Izmitli
Aslin
A
de Pablo
J J
JJ
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D014199:Trehalose / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D016229:Amyloid beta-Peptides; D008051:Lipid Bilayers; D010446:Peptide Fragments; C419409:amyloid beta-protein (29-40); D014867:Water; D014199:Trehalose