Recent progress and future directions of the research on nanoplastic-induced neurotoxicity.

Many types of plastic products, including polystyrene, have long been used in commercial and industrial applications. Microplastics and nanoplastics, plastic particles derived from these plastic products, are emerging as environmental pollutants that can pose health risks to a wide variety of living organisms, including humans. However, it is not well understood how microplastics and nanoplastics affect cellular functions and induce stress responses. Humans can be exposed to polystyrene-microplastics and polystyrene-nanoplastics through ingestion, inhalation, or skin contact. Most ingested plastics are excreted from the body, but inhaled plastics may accumulate in the lungs and can even reach the brain via the nose-to-brain route. Small-sized polystyrene-nanoplastics can enter cells by endocytosis, accumulate in the cytoplasm, and cause various cellular stresses, such as inflammation with increased pro-inflammatory cytokine production, oxidative stress with generation of reactive oxygen species, and mitochondrial dysfunction. They induce autophagy activation and autophagosome formation, but autophagic flux may be impaired due to lysosomal dysfunction. Unless permanently exposed to polystyrene-nanoplastics, they can be removed from cells by exocytosis and subsequently restore cellular function. However, neurons are very susceptible to this type of stress, thus even acute exposure can lead to neurodegeneration without recovery. This review focuses specifically on recent advances in research on polystyrene-nanoplastic-induced cytotoxicity and neurotoxicity. Furthermore, in this review, based on mechanistic studies of polystyrene-nanoplastics at the cellular level other than neurons, future directions for overcoming the negative effects of polystyrene-nanoplastics on neurons were suggested.