This study investigates the molecular effects of 30 nm polystyrene (PS) nanoplastics (NPs) on human neural stem cells (hNS1) after 4 days of exposure at concentrations of 0.5, 2.5, and 10 μg/mL. The results show that PS NPs induce oxidative stress, cellular stress, DNA damage, inflammatory response alterations, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases. The study analyzed gene expression of various metabolic pathways, including stress response (hsp27/hspB1, hsp60, hsp70/hspA5, and hsp90α), DNA repair (xrcc1, gad45a, rad51), oxidative damage response (Cu/ZnSOD 1, MnSOD 2), apoptotic response (Cas3a, Cas7, p53, Bcl2), and mitochondrial response (Cox5A), as biomarkers of NP damage. PS NPs increased the expression of hsp27/hspB1 and hsp90α mRNA, while inhibiting hsp70/hspA5 mRNA expression. These findings suggest that PS NPs alter the cellular response to stress in human neural cells. Additionally, PS NPs activated the expression of Cu/ZnSOD1 and catalase (CAT), indicating an oxidative stress response. The study also found that PS NPs increased the expression of gadd45α and rad51, which are involved in DNA repair, while decreasing xrcc1 expression, suggesting DNA damage. PS NPs also induced apoptosis by increasing the expression of Cas7 and Bcl2, and decreasing the expression of Cas3α and p53. The study further showed that PS NPs induced inflammatory responses by altering the expression of TNFα, IL-6, and IL-8. The results indicate that PS NPs can cause damage and functional alterations in human neuronal cells, highlighting the need for further research on the effects of NPs on neurodevelopmental and neurodegenerative diseases.This study investigates the molecular effects of 30 nm polystyrene (PS) nanoplastics (NPs) on human neural stem cells (hNS1) after 4 days of exposure at concentrations of 0.5, 2.5, and 10 μg/mL. The results show that PS NPs induce oxidative stress, cellular stress, DNA damage, inflammatory response alterations, and apoptosis, which could lead to tissue damage and neurodevelopmental diseases. The study analyzed gene expression of various metabolic pathways, including stress response (hsp27/hspB1, hsp60, hsp70/hspA5, and hsp90α), DNA repair (xrcc1, gad45a, rad51), oxidative damage response (Cu/ZnSOD 1, MnSOD 2), apoptotic response (Cas3a, Cas7, p53, Bcl2), and mitochondrial response (Cox5A), as biomarkers of NP damage. PS NPs increased the expression of hsp27/hspB1 and hsp90α mRNA, while inhibiting hsp70/hspA5 mRNA expression. These findings suggest that PS NPs alter the cellular response to stress in human neural cells. Additionally, PS NPs activated the expression of Cu/ZnSOD1 and catalase (CAT), indicating an oxidative stress response. The study also found that PS NPs increased the expression of gadd45α and rad51, which are involved in DNA repair, while decreasing xrcc1 expression, suggesting DNA damage. PS NPs also induced apoptosis by increasing the expression of Cas7 and Bcl2, and decreasing the expression of Cas3α and p53. The study further showed that PS NPs induced inflammatory responses by altering the expression of TNFα, IL-6, and IL-8. The results indicate that PS NPs can cause damage and functional alterations in human neuronal cells, highlighting the need for further research on the effects of NPs on neurodevelopmental and neurodegenerative diseases.