EFFECT OF CARBONACEOUS NANOPARTICLES ON THE STRUCTURE AND OLIGOMERIZATION OF AΒ42

Particulate air pollution is an environmental problem recognized as a global public health issue such as Alzheimer's disease (AD)-type dementia. Although the toxicological effects of environmental particle matter (PM) have been reported, the mechanism underlying the effect of PM on protein conformational changes, which are associated with the development of various diseases, has yet to be elucidated. In this study, molecular dynamics simulations were performed to investigate the impact of carbonaceous nanoparticles on the structure of the Aβ42 monomer and the oligomerization of four Aβ42 peptides, associated with the development of AD. For the simulations, a fullerene (C60) was used for the modeling of elemental carbon (EC), while benzo[a]pyrene (B[a]P) was used for the modeling of organic carbon. The results revealed that the presence of C60 accelerated the tetramerization of Aβ42 peptides by 2.5 times, while C60/B[a]P promoted the unfolding of the peptide monomer showing the strongest interactions with the Aβ42 monomer. Similarly, C60/4B[a]P decreased the number of helices in the secondary structure of the peptide monomer by 60%. The simplified nanoparticle models in this study promote the early aggregation of peptides to dimers, suggesting the progression of AD. In vivo studies focusing on protein structural changes and aggregation due to long-term exposure to PM/nanoparticles will be of interest for developing strategies of prevention and treatment of AD.