Effect of ambient polycyclic aromatic hydrocarbons and nicotine on the structure of Aβ₄₂ protein

Highlights

● B[a]P, nicotine and phenanthrene molecules altered the secondary structure of Aβ₄₂.

● β-content of the peptide was significantly enhanced in the presence of the PAHs.

● Nicotine made stable cluster with Aβ₄₂ peptide via hydrogen bonds.

● Phenanthrene due to its small size, interfered with the Aβ₄₂ monomer more strongly.

Abstract

Recent studies have correlated the chronic impact of ambient environmental pollutants like polycyclic aromatic hydrocarbons (PAHs) with the progression of neurodegenerative disorders, either by using statistical data from various cities, or via tracking biomarkers during in-vivo experiments. Among different neurodegenerative disorders, PAHs are known to cause increased risk for Alzheimer’s disease, related to the development of amyloid beta (Aβ) peptide oligomers. However, the complex molecular interactions between peptide monomers and organic pollutants remains obscured. In this work, we performed an atomistic molecular dynamics study via GROMACS to investigate the structure of Aβ₄₂ peptide monomer in the presence of benzo[a]pyrene, nicotine, and phenanthrene. Interestingly the results revealed strong hydrophobic, and hydrogen-bond based interactions between Aβ peptides and these environmental pollutants that resulted in the formation of stable intermolecular clusters. The strong interactions affected the secondary structure of the Aβ₄₂ peptide in the presence of the organic pollutants, with almost 50 % decrease in the α-helix and 2 %–10 % increase in the β-sheets of the peptide. Overall, the undergoing changes in the secondary structure of the peptide monomer in the presence of the pollutants under the study indicates an enhanced formation of Aβ peptide oligomers, and consequent progression of Alzheimer’s disease.

Graphical abstract

Keywords

Polycyclic aromatic hydrocarbons / Nicotine / toxicology / Aβ₄₂ peptide / Alzheimer’s disease / Molecular dynamics simulations / Environmental pollution

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Acknowledgements

The research was conducted under the project “OPCRP2022003 Exposure to Cooking Ultrafine Particles and Neurodegenerative Disease: Clinical Exposure Studies and Computer Modeling” and “11022021FD2905 Efficient thermal valorization of municipal sewage sludge in fluidized bed systems: Advanced experiments with process modeling”.

We thank Dr. Jianguo Li for his valuable support and insightful comments in this work.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11783-023-1615-2 and is accessible for authorized users.

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