Inhibition of Aβ Aggregation by [TEA][Ms] Follows Weakening of the Hydrophobic Core and Sequestration of Peptides in Ionic Liquid Nanodomains.

We developed a coarse-grained model for the protic ionic liquid, triethylammonium mesylate ([TEA][Ms]), to characterize its inhibitory effects on amyloid aggregation using the KLVFFAE fragment of the amyloid-β (Aβ) as a model amyloidogenic peptide. In agreement with previous experiments, coarse-grained molecular dynamics simulations showed that increasing concentrations of [TEA][Ms] in aqueous media led to increasingly small Aβ aggregates with low beta-sheet contents. The cause of [TEA][Ms]'s inhibition of peptide aggregation was found to be a result of two interrelated effects.

Unravelling heparin's enhancement of amyloid aggregation in a model peptide system.

A coarse-grained (CG) model for heparin, an anionic polysaccharide, was developed to investigate the mechanisms of heparin's enhancement of fibrillation in many amyloidogenic peptides. CG molecular dynamics simulations revealed that heparin, by forming contacts with the model amyloidogenic peptide, amyloid-β's KLVFFAE fragment (Aβ), promoted long-lived and highly beta-sheet-like domains in the peptide oligomers. Concomitantly, heparin-Aβ contacts suppressed the entropy of mixing of the oligomers' beta-domains.

Mechanistic insights into the inhibition of amyloid-β aggregation by chitosan.

Neurodegeneration related to Alzheimer's disease has long been linked to the accumulation of abnormal aggregates of amyloid-β (Aβ) peptides. Pre-fibrillar oligomeric intermediates of Aβ aggregation are considered the primary drivers of neurotoxicity, however, their targetting remains an unresolved challenge. In response, the effects of macromolecular components of the blood-brain barrier, artificial extracellular matrix mimics, and polymeric drug delivery particles, on the aggregation of Aβ peptides are gaining interest.