Exposure to polycyclic aromatic hydrocarbons promotes the progression of Alzheimer's disease

Polycyclic aromatic hydrocarbons (PAHs) are typical organic compounds found in cigarette smoke and vehicle exhaust. In addition, PAHs are produced from incomplete combustion of organic material and cooking. The highest concentrations of PM-bound PAHs ranged from 550 ng/m3 to 39000 ng/m3, were observed in Chinese kitchens, fire stations, and ships. Polycyclic aromatic hydrocarbons may combine with ultrafine particles (UFPs) in the air to form particle-bound PAHs. PM0.1 may adsorb large amounts of toxic organic compounds, and long-term exposure to indoor UFPs from cooking resulted in nervous responses by the human brain. PAHs were detected in the venous blood of people exposed to combustion by-products in rural areas of China at concentrations up to 762 ng/mL.

Aβ peptide contains various isoforms, with 42 aminoacids in its structure, is more abundant in human cerebrospinal fluid. It had been shown that chronic exposure of fish to benzo[a]pyrene (B[a]P) resulted in increased concentrations of Aβ42 peptide in the brain, leading to a decrease in their cognitive behavior, memory locomotor and motor activity. Aβ oligomers may contribute to the development of Alzheimer's Disease (AD) by damaging neurons and disrupting electrochemical signals. Polycyclic aromatic hydrocarbons including phenanthrene, pyrene and B[a]P increased the aggregation kinetics of Aβ-peptide. Although the aggregation of Aβ peptides and the formation of oligomers are enhanced in the presence of PAHs, what are the molecular interactions between Aβ polypeptides and PAHs?

To answer this question, researchers from Nazarbayev University, Tokyo University of Science and their teams collaborated to explore and reveal the effect of polycyclic aromatic hydrocarbons as the major compounds of cooking particles on the structure of Aβ42 peptide. Their study reveals that Aβ polypeptides interact strongly with polycyclic aromatic hydrocarbons of different properties, and that these organic pollutants alter the structure of Aβ42 and promote the progression of Alzheimer's Disease. This study entitled "Effect of ambient polycyclic aromatic hydrocarbons and nicotine on the structure of Aβ42 protein" is published online in Frontiers of Environmental Science & Engineering in 2023.

In this study, the research team found that the structure of Aβ42 peptide monomer was affected by benzo[a]pyrene, nicotine and phenanthrene molecules, depending on their hydrophobicity, size, and H-bonding capacity. The secondary structure of Aβ42 peptide was changed by organic pollutants, with almost 50 % decrease in the α-helix and 2 %–10 % increase in the β-sheets of the peptide. Their results also suggested that benzo[a]pyrene, nicotine, and phenanthrene might have effect on the progression of Alzheimer's Disease.

This study successfully conducted atomic and molecular dynamics studies using GROMACS to study the structure of Aβ42 peptide monomer in the presence of benzo [a] pyrene, nicotine and phenanthrene. This work not only analyzed the effects of organic pollutants on the results of Aβ peptide monomer at the molecular level, but also provided guidance for the treatment of Alzheimer's disease, and increased attention to the neurodegenerative disorders caused by air pollution.

Journal reference:

Kaumbekova, S., et al. (2022). Effect of ambient polycyclic aromatic hydrocarbons and nicotine on the structure of Aβ42 protein. Frontiers of Environmental Science & Engineering. doi.org/10.1007/s11783-023-1615-2.


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