Although cigarette aerosol exposure is associated with various adverse health issues, its impact on Parkinson’s disease (PD) remains elusive. Here, we investigated the effect of cigarette aerosol extract (CAE) on SH-SY5Y cells for the first time, both with and without α-synuclein (α-Syn) overexpression. We found that α-Syn aggravates CAE-induced cell death, oxidative stress, and mitochondrial dysfunction. Fluorescence cross-correlation spectroscopy (FCCS) revealed a dual distribution of α-Syn within the cells, with homogeneous regions indicative of monomeric α-Syn and punctated regions, suggesting the formation of oligomers. Moreover, we observed colocalization of α-Syn oligomers with lysosomes along with a reduction in autophagy activity. These findings suggest that α-Syn overexpression exacerbates CAE-induced intracellular cytotoxicity, mitochondrial dysfunction, and autophagy dysregulation, leading to elevated cell mortality. Our findings provide new insights into the pathogenic mechanisms linking exposure to cigarette aerosols with neurodegenerative diseases.

中文翻译：

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香烟气溶胶对 SH-SY5Y 中 α-突触核蛋白寡聚化和细胞活力的影响：对帕金森病的影响

尽管接触香烟气溶胶与各种不良健康问题有关，但其对帕金森病 (PD) 的影响仍然难以捉摸。在这里，我们首次研究了香烟气溶胶提取物 (CAE) 对有和没有 α-突触核蛋白 (α-Syn) 过表达的 SH-SY5Y 细胞的影响。我们发现 α-Syn 会加剧 CAE 诱导的细胞死亡、氧化应激和线粒体功能障碍。荧光互相关光谱 (FCCS) 显示细胞内 α-Syn 的双重分布，均匀区域表示单体 α-Syn，而点状区域则表明寡聚体的形成。此外，我们观察到 α-Syn 寡聚物与溶酶体的共定位以及自噬活性的降低。这些发现表明，α-Syn 过度表达会加剧 CAE 诱导的细胞内细胞毒性、线粒体功能障碍和自噬失调，导致细胞死亡率升高。我们的研究结果为接触香烟气溶胶与神经退行性疾病之间的致病机制提供了新的见解。