Effect of carbonaceous ultrafine particles on the structure and oligomerization of Aß42 peptide.

The impact of pervasive air pollutants on human health is a growing concern in scientific communities. Among different air pollutants, ultrafine particles (UFPs; with aerodynamic diameter <100 nm) might pass through biological barriers and have a severe impact on human health, including early progression of neurodegenerative diseases such as Alzheimer's disease (AD). A significant fraction of UFPs consists of carbonaceous compounds, composed of elemental and organic carbon (EC and OC). While in-vivo experimental studies showed the neurotoxicity of typical OC and polycyclic aromatic hydrocarbons (PAHs), the molecular interactions involved in the progression of AD remain unclear. In this study, molecular dynamics simulations were performed to investigate the impact of carbonaceous UFPs on the structure of the Aß42 monomer and the oligomerization of four Aß42 peptides, associated with the development of AD. For the simulations, a fullerene (C60) was used for the modeling of EC, while benzo [a]pyrene (B[a]P) was used for the modeling of OC. The results revealed that the presence of C60 accelerated the tetramerization of Aß42 peptides by 2.5 times, while C60/B[a]P promoted the unfolding of the peptide monomer showing the strongest interactions with the Aß42 monomer. Similarly, C60/4B[a]P decreased the number of helices in the secondary structure of the peptide monomer by 60%. The simplified UFP models in this study, promoted the early aggregation of peptides to dimers, suggesting the progression of AD.

Ambient Benzo[a]pyrene's Effect on Kinetic Modulation of Amyloid Beta Peptide Aggregation: A Tentative Association between Ultrafine Particulate Matter and Alzheimer's Disease.

Long-time exposure to ambient ultrafine particles is associated with an increased risk of neurodegenerative diseases such as Alzheimer's disease (AD), which is triggered by the aggregation of Aß peptide monomers into toxic oligomers. Among different ultrafine air pollutants, polycyclic aromatic hydrocarbons (PAHs) are known to have a negative neural impact; however, the impact mechanism remains obscure. We herein examined the effect of Benzo[a]Pyrene (B[a]P), one of the typical PAHs on Aß42 oligomerization using all-atom molecular dynamics simulations. In particular, the simulations were performed using four molecules of Aß42 in the presence of 5.00 mM, 12.5 mM, and 50.0 mM of B[a]P. The results revealed strong hydrophobic interactions between Aß42 peptides and B[a]P, which in turn resulted in increased interpeptide electrostatic interactions. Furthermore, 5.00 mM of B[a]P accelerated the kinetics of the formation of peptide tetramer by 30%, and stabilized C-terminus in Aß42 peptides, suggesting consequent progression of AD in the presence of 5.00 mM B[a]P. In contrast, 12.5 mM and 50.0 mM of B[a]P decreased interpeptide interactions and H-bonding due to the aggregation of numerous B[a]P clusters with the peptides, suppressing oligomerization kinetics of Aß42 peptides by 13% and 167%, respectively. While the study elucidates the effect of small environmental hydrophobic molecules on the formation of Aß oligomers, the impact of ambient ultrafine particles on AD in the complex composition of the environmental realm requires further systematic delving into the field.

Changes in the Secondary Structure and Assembly of Proteins on Fluoride Ceramic (CeF3) Nanoparticle Surfaces.

Fluoride nanoparticles (NPs) are materials utilized in the biomedical field for applications including imaging of the brain. Their interactions with biological systems and molecules are being investigated, but the mechanism underlying these interactions remains unclear. We focused on possible changes in the secondary structure and aggregation state of proteins on the surface of NPs and investigated the principle underlying the changes using the amyloid ß peptide (Aß16-20) based on infrared spectrometry. CeF3 NPs (diameter 80 nm) were synthesized via thermal decomposition. Infrared spectrometry showed that the presence of CeF3 NPs promotes the formation of the ß-sheet structure of Aß16-20. This phenomenon was attributed to the hydrophobic interaction between NPs and Aß peptides in aqueous environments, which causes the Aß peptides to approach each other on the NP surface and form ordered hydrogen bonds. Because of the coexisting salts on the secondary structure and assembly of Aß peptides, the formation of the ß-sheet structure of Aß peptides on the NP surface was suppressed in the presence of NH4+ and NO3- ions, suggesting the possibility that Aß peptides were adsorbed and bound to the NP surface. The formation of the ß-sheet structure of Aß peptides was promoted in the presence of NH4+, whereas it was suppressed in the presence of NO3- because of the electrostatic interaction between the lysine residue of the Aß peptide and the ions. Our findings will contribute to comparative studies on the effect of different NPs with different physicochemical properties on the molecular state of proteins.

Impact of ultrafine particles and secondary inorganic ions on early onset and progression of amyloid aggregation: Insights from molecular simulations.

Alzheimer's disease (AD) is a neurodegenerative disorder, associated with the aggregation of amyloid beta (Aß) peptides and formation of plaques. The impact of airborne particulate matter (PM) and ultrafine particles (UFPs), on early onset and progression of AD has been recently hypothesized. Considering their small size, carbon black nanoparticles and UFPs can penetrate into human organism and affect Alzheimer's progression. While experiments show that the exposure of PM and UFPs can lead to enhanced concentrations of Aß peptides, the interactions between the peptides and UFPs remain obscured. Particularly, the impact of UFPs on the initial rate of aggregation of the peptides is ambiguous. Herein, we perform molecular dynamics simulations to investigate the aggregation of Aß16-21 peptides, an aggregation-prone segment of Aß, in the presence of UFPs, mimicked by C60, under different salt solutions suggesting the presence of the inorganic constituents of PM in the blood. In particular, the simulations were performed in the presence of Na+, Cl- and CO3-2 ions to characterize typical buffer environments and electrolytes present in human blood. Furthermore, NH4+, NO3- and SO4-2 ions, found in PM, were used in the simulations. The results revealed high propensity for the aggregation of Aß16-21 peptides. Moreover, the peptides made clusters with C60 molecules, that would be expected to act as a nucleation site for the formation of amyloid plaques. Taken together, the results showed that UFPs affected the peptide aggregation differently, depending on the type of ions present in the simulation environment. In the presence of C60, SO4-2 and NO3- ions accelerated the aggregation of Aß16-21 peptides, however, NH4+ ions decelerated their aggregation. In addition, UFP lowered ß-sheets amounts at all environments, except NaCl solution.