Modeling of the Inhibitory Effect of Nanoparticles on Amyloid β Fibrillation

Abstract

Experiments have shown that charged nanoparticles (NP) inhibit, partially or completely, the aggregation of Aβ protein monomers into fibrils. The equilibrium fibril content is found to be inversely proportional to the concentration of NP. In this work, we report a kinetic model for the fibrillation of Aβ protein in the presence of NP. In the model, apart from nucleation, elongation and fragmentation processes, the effect of NP is considered to cause a conformational change to the protein monomer, making the latter incompatible for aggregation. The simulated results explain the growth kinetics of pure Aβ (1-40) protein, and the kinetics in the presence of NP. The NP-monomer interaction considered in the model captures the significant effect of NP on the fibrillation process at a very molar ratio (NP to Aβ monomer) as low as 10. The model predictions are compared with two different NP systems, namely, gold and silica NP. The model can be applied to explain the inhibitory effect of other additives such as small molecules, NP, lipids, and surfactants that show a similar inhibition trend for fibril formation of Aβ and other proteins.

Polyphenol capping on a gold nanosurface modulates human serum albumin fibrillation

“…Gold nanoparticles are known to enhance polyphenol solubilisation and diffusive adsorption at protein interfaces. 58,59 Polyphenols like quercetin ionize extensively at pH 7.4, but that was minimal in the case of silymarin. The different inhibitory effect of AuNPs on HSA fibrillation was likely due to similar effects.…”

Self-Assembled Curcumin–Poly(carboxybetaine methacrylate) Conjugates: Potent Nano-Inhibitors against Amyloid β-Protein Fibrillogenesis and Cytotoxicity

“…Until now, many inhibitors against Aβ aggregation and amyloid toxicity have been reported, including peptides, − small organic molecules, − nanoparticles (NPs), − and proteins. − Among these inhibiting agents, small organic molecules such as epigallocatechin gallate and curcumin were identified to show potent inhibitory effects. , Especially, curcumin has both obvious inhibiting capacity on Aβ fibrillogenesis and disaggregation effect on mature fibrils. , Nevertheless, there are significant drawbacks that limit its application. For example, curcumin has extremely low solubility in aqueous solution (0.27 μg/mL) and low stability in serum which results in its rapid clearance from blood. , To solve these problems that vitally limit its bioavailability, several approaches including codelivery with nanoparticles and modification as prodrugs have been proposed. , Among the approaches, conjugating curcumin to polymers has attracted great attention, owing to their readily tailorable chemical structure.…”

Polyoxometalates as Effective Nano-inhibitors of Amyloid Aggregation of Pro-inflammatory S100A9 Protein Involved in Neurodegenerative Diseases

“…Despite significant efforts over the past decades, there are still no drugs available to avert amyloid neurodegenerative disease progression and the overall failure rate in the clinical trials is very high even for compounds that have shown promising anti-amyloid activity in vitro . Various inhibitors have been developed for arresting or modulating the amyloid aggregation, including peptides and peptidomimetics, 59 , 60 nanoparticles, 61 chaperons, 62 and molecular tweezers. 63 Among them, antibodies 64 , 65 have received significant attention due to their high specificity toward their targets, despite their relatively high production cost.…”