Polystyrene nanoparticles trigger aberrant condensation of TDP-43 and amyotrophic lateral sclerosis-like symptoms

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 nano-size 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. Additionally, 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 TDP-43’s condensation and solidification. 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. To investigate the effects of the environmental particle pollutant polystyrene nanoplastics on brain damage, we established a mouse inhalation model by continuously intranasally exposing male C57BL/6J mice. We then performed gene expression profiling using RNA-seq data from whole brain tissues of mice in the unexposed and exposed groups. Comparative gene expression profiling analysis of RNA-seq data of whole brain tissues of mice in unexposed and exposed groups.