TY - JOUR
T1 - Effect of carbonaceous ultrafine particles on the structure and oligomerization of Aβ42 peptide
AU - Kaumbekova, Samal
AU - Amouei Torkmahalleh, Mehdi
AU - Umezawa, Masakazu
AU - Wang, Yanwei
AU - Shah, Dhawal
N1 - Funding Information:
This research is funded by Nazarbayev University under Collaborative Research Program Grant No 11022021CRP1503 awarded to DS and MAT “Exposure to Cooking Ultrafine Particles and Neurodegenerative Disease: Clinical Exposure Studies and Computer Modeling”.
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/4/15
Y1 - 2023/4/15
N2 - 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 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 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 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 UFP models in this study, promoted the early aggregation of peptides to dimers, suggesting the progression of AD.
AB - 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 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 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 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 UFP models in this study, promoted the early aggregation of peptides to dimers, suggesting the progression of AD.
KW - Alzheimer's diseases
KW - Amyloid beta peptide
KW - Carbonaceous ultrafine particles
KW - Environmental nanotoxicology
KW - Oligomerization
KW - Protein structure
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U2 - 10.1016/j.envpol.2023.121273
DO - 10.1016/j.envpol.2023.121273
M3 - Article
C2 - 36780974
AN - SCOPUS:85150226113
SN - 0269-7491
VL - 323
JO - Environmental Pollution
JF - Environmental Pollution
M1 - 121273
ER -