Kaumbekova Samal, Amouei Torkmahalleh Mehdi, Umezawa Masakazu, Wang Yanwei, Shah Dhawal
Department of Chemical and Materials Engineering, School of Engineering and Digital Sciences, Nazarbayev University, Kabanbay Batyr 53, Astana, 010000, Kazakhstan.
Division of Environmental and Occupational Health Sciences, School of Public Health, University of Illinois at Chicago, Chicago, IL, 60612, USA.
Environ Pollut. 2023 Apr 15;323:121273. doi: 10.1016/j.envpol.2023.121273. Epub 2023 Feb 11.
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 Aβ monomer and the oligomerization of four Aβ peptides, associated with the development of AD. For the simulations, a fullerene (C) 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 C accelerated the tetramerization of Aβ peptides by 2.5 times, while C/B[a]P promoted the unfolding of the peptide monomer showing the strongest interactions with the Aβ monomer. Similarly, C/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.
空气中普遍存在的污染物对人类健康的影响日益受到科学界的关注。在不同的空气污染物中，超细颗粒（UFPs；空气动力学直径<100纳米）可能会穿过生物屏障，对人类健康产生严重影响，包括阿尔茨海默病（AD）等神经退行性疾病的早期进展。相当一部分超细颗粒由含碳化合物组成，包括元素碳和有机碳（EC和OC）。虽然体内实验研究表明典型的有机碳和多环芳烃（PAHs）具有神经毒性，但AD进展过程中涉及的分子相互作用仍不清楚。在本研究中，进行了分子动力学模拟，以研究含碳超细颗粒对Aβ单体结构以及与AD发展相关的四种Aβ肽寡聚化的影响。在模拟中，用富勒烯（C）对元素碳进行建模，用苯并[a]芘（B[a]P）对有机碳进行建模。结果表明，C的存在使Aβ肽的四聚化加速了2.5倍，而C/B[a]P促进了与Aβ单体相互作用最强的肽单体的解折叠。同样，C/4B[a]P使肽单体二级结构中的螺旋数量减少了60%。本研究中简化的超细颗粒模型促进了肽向二聚体的早期聚集，提示了AD的进展。
