Effect of trehalose on amyloid β (29–40)-membrane interaction.

A growing body of experimental evidence indicates that the interaction between amyloid β 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 β peptide. Molecular simulations are used to examine the effect of trehalose on the conformational stability of amyloid β peptide in aqueous solution and its effect on the interaction between amyloid β 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 β peptide into a membrane is more favorable when the peptide is folded into an α-helix than in a random coil conformation, thereby suggesting that trehalose promotes the insertion of α-helical amyloid β into biological membranes. [ABSTRACT FROM AUTHOR]