From the Environment to Molecular Interactions of Nanoplastics: Unraveling the Neurotoxic Impacts and the Implications in Neurodegenerative Processes

Nanoplastics (NPs) represent an escalating hazard to both humans and the ecosystem due to their pervasive presence. This review delves into (i) the widespread occurrence of NPs across the different environmental matrices, including food; (ii) routes and estimates for human exposure; (iii) the mechanisms of blood–brain barrier (BBB) crossing; and (iv) implications for human health, with a specific focus on molecular features associated with neurotoxicity and neurodegenerative processes. The impact of NPs on the central nervous system, their ability to cross the BBB and the underpinning mechanisms, the potential to initiate neurotoxicity by fostering β-amyloid aggregation, and their interactions with metallo-enzymes (such as superoxide dismutase) are elucidated. The analysis of transcriptomics and epigenomic results, including microRNA dysregulation, unveil how NPs could contribute to neurological disorders. The need for considering overlaps among diverse pathogenetic mechanisms when probing the effects of NPs is discussed. Additional urgent needs are the development of reliable in vitro models for neurotoxicity studies able to mimic the complexity of the nervous system and the exposure of such models to more environmentally relevant NPs. Finally, the development of extremely sensitive detection and analysis methodologies to quantify NPs in environmental and biological matrices is a pressing priority.