Nanoparticles and neurodegeneration: Insights on multiple pathways of programmed cell death regulated by nanoparticles

Currently, nanoparticles (NPs) are extensively applied in the diagnosis and treatment of neurodegenerative diseases (NDs). With the rapid development and increasing exposure to the public, the potential neurotoxicity associated with NDs caused by NPs has attracted the researchers' attentions but their biosafety assessments are still far behind relevant application studies. Based on recent research, this review aims to conduct a comprehensive and systematic analysis of neurotoxicity induced by NPs. The 191 studies selected according to inclusion and exclusion criteria were imported into the software, and the co-citations and keywords of the included literatures were analyzed to find the breakthrough point of previous studies. According to the available studies, the routes of NPs entering into the normal and injured brain were various, and then to be distributed and accumulated in living bodies. When analyzing the adverse effects induced by NPs, we focused on multiple programmed cell deaths (PCDs), especially ferroptosis triggered by NPs and their tight connection and crosstalk that have been found playing critical roles in the pathogenesis of NDs and their underlying toxic mechanisms. The activation of multiple PCD pathways by NPs provides a scientific basis for the occurrence and development of NDs. Furthermore, the adoption of new methodologies for evaluating the biosafety of NPs would benefit the next generation risk assessment (NGRA) of NPs and their toxic interventions. This would help ensure their safe application and sustainable development in the field of medical neurobiology.