Abstract
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 Aβ 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 Aβ42 oligomerization using all-atom molecular dynamics simulations. In particular, the simulations were performed using four molecules of Aβ42 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 Aβ42 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 Aβ42 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 Aβ42 peptides by 13% and 167%, respectively. While the study elucidates the effect of small environmental hydrophobic molecules on the formation of Aβ oligomers, the impact of ambient ultrafine particles on AD in the complex composition of the environmental realm requires further systematic delving into the field.