Stability of Aβ-fibril fragments in the presence of fatty acids

Abstract

We consider the effect of lauric acid on the stability of various fibril-like assemblies of Aβ peptides. For this purpose, we have performed molecular dynamics simulations of these assemblies either in complex with lauric acid or without presence of the ligand. While we do not observe a stabilizing effect on Ab40-fibrils we find that addition of lauric acid strengthen the stability of fibrils built from the more toxic triple-stranded S-shaped Ab42-peptides. Or results may help to understand how specifics of the brain-environment modulate amyloid formation and propagation.

Effect of Lauric Acid on the Stability of Aβ42-Oligomers

“…-d. On the other hand, no stabilizing effect is seen when considering only the native contacts.Similar to what was seen by us in earlier work,6 the ring-like oligomers of Model A type decay even in the presence of lauric acid and for in-register arrangement of the β 2 and β 3 strands much faster than the experiments in the Rangachari lab would let one expect. The situation is worse for Model B, where the individual chains take a form as seen in the Cryo-EM model (PDB ID: 5OQV)20 of an Aβ 42 fibril.…”

“…Surprisingly, we did not find in Ref. 6 a stabilization of this structure by the presence of lauric acid. For this reason, we have considered in the present study not only this model, but also the one where in the individual chains the β 2 and β 3 strands are in an out-of-register arrangement (ORF), replacing the inter-chain hydrogen bonds of the IRF geometry by intrahydrogen bonds.…”

“…[3][4][5] In Ref. 6 we could indeed demonstrate that addition of lauric acid raises fibril stability for Aβ 42 , while no such stabilizing effect was found for Aβ 40 fibrils. Our results further suggested that presence of lauric acid enhances the elongation of Aβ 42 -fibrils but not their nucleation.…”