Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the dysfunction and progressive death of cerebral and spinal motor neurons. Preliminary epidemiological research has hinted at a relationship between environmental risks and the escalation of ALS, but the underlying reasons remain mostly mysterious. Here we show that nanosize polystyrene plastics (PS) induce ALS-like symptoms and illustrate the related molecular mechanism. When exposed to PS, cells endure internal oxidative stress, which leads to the aggregation of TAR DNA-binding protein 43 kDa (TDP-43), triggering ALS-like characteristics. In addition, the oxidized heat shock protein 70 fails to escort TDP-43 back to the nucleus. The cytoplasmic accumulation of TDP-43 facilitates the formation of a complex between PS and TDP-43, enhancing the condensation and solidification of TDP-43. These findings are corroborated through in silico and in vivo assays. Altogether, our work illustrates a unique toxicological mechanism induced by nanoparticles and provides insights into the connection between environmental pollution and neurodegenerative disorders.

肌萎缩侧索硬化症（ALS）是一种神经退行性疾病，其特征是大脑和脊髓运动神经元功能障碍和进行性死亡。初步流行病学研究已暗示环境风险与 ALS 升级之间存在关联，但其根本原因仍然是个谜。在这里，我们证明纳米级聚苯乙烯塑料 (PS) 会诱发类似 ALS 的症状，并说明相关的分子机制。当暴露于 PS 时，细胞会承受内部氧化应激，导致 TAR DNA 结合蛋白 43 kDa (TDP-43) 聚集，引发类似 ALS 的特征。此外，氧化的热休克蛋白70无法护送TDP-43回到细胞核。 TDP-43在细胞质中的积累有利于PS和TDP-43之间形成复合物，从而增强TDP-43的凝聚和凝固。这些发现通过计算机和体内测定得到证实。总而言之，我们的工作阐明了纳米颗粒诱导的独特毒理学机制，并提供了对环境污染与神经退行性疾病之间联系的见解。