## 7 Molecular Effects of Nanoplastics in Processes of Neurotoxicity  
### Neurodegeneration  
Environmental and food data are largely available on MPs and MNPs rather than NPs. In fact, the detection in environmental samples and even more in human tissues and organs of smaller-sized plastic particles (NPs) is currently limited by technology, which should be improved for a better understanding of NPs' burdens in terms of quantities and polymer type. However, due to recent data that demonstrate the ability of NPs to pass barriers and exert (neuro)toxicological effects, the following sections are specifically dedicated to the \begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Plastic Particle Size** & **Plastic Type** & **Model Used** & **Target and Effect** & **Reference** \\ \hline
5 nm & PS & Computational model & Gastrointestinal barrier and BBB crossing & [8] \\ \hline
30–50 nm & PS & Mouse & Brain accumulation (hippocampus) & [113] \\ \hline
30–50 nm & PS & Rat primary culture of microglia &
\begin{tabular}{c} Internalization, microglia activation, \\ and neuroinflammation \\ \end{tabular} & [113] \\ \hline
25 and 50 nm & PS & Pregnant rat &
\begin{tabular}{c} Transgenerational accumulation in the \\ brains of fetuses \\ \end{tabular} & [125] \\ \hline
50 nm & PS & \
\begin{tabular}{c} RBL-2H3 cells (rat basophilic \\ leukemia cells) \\ \end{tabular} &
\begin{tabular}{c} Cell membrane crossing and delivery \\ to lysosomes \\ \end{tabular} & [103] \\ \hline
50 nm & PS & Mouse & Brain accumulation & [115] \\ \hline
50 nm & PS & \
\begin{tabular}{c} hCMEC/D3 human cerebral \\ microvascular endothelial cells \\ (BBB model) \\ \end{tabular} &
\begin{tabular}{c} Internalization, tight junction disturbance, \\ decreased occludin \\ expression, necrotosis \\ \end{tabular} & [115] \\ \hline
50 nm & PS & Mouse &
\begin{tabular}{c} Increased permeability and \\ BBB disruption \\ \end{tabular} & [114] \\ \hline
50 nm & PS & \
\begin{tabular}{c} Mouse b.End.3 endothelial cells \\ (BBB model) \\ \end{tabular} &
\begin{tabular}{c} BBB disruption by \\ feroprotosis contribution \\ \end{tabular} & [114] \\ \hline
100 nm & PS & \
\begin{tabular}{c} Mouse hippocampal neuronal \\ HT22 cells \\ \end{tabular} &
\begin{tabular}{c} Internalization and decreased viability \\ \end{tabular} & [117] \\ \hline
293 nm * & PS & Mouse & Presence of particles in brain tissues & [8] \\ \hline \hline \end{tabular}  
* Referred to by the authors as NPs.  
\end{table} 
Table 1: Overview of nanoplastic particles’ effects on the blood–brain barrier (BBB) and on brain accumulation in computational and mammalian in vivo and in vitro models. neurootoxic and possible neurodegenerative effects of NPs. Therefore, the focus is on NPs which are able to pass the BBB, as described in Section 6 and summarized in Table 1, and to affect brain and neuron functions. In Vitro and In Silico Interaction of Nanoplastics with Superoxide Dismutase and Amyloid Protein Formation: Implications for Oxidative Stress and Neurodegeneration  
The central nervous system (CNS) is particularly susceptible to oxidative imbalance owing to its abundance of polyunsaturated fatty acids, high metabolic oxidative rate, and elevated content of transient metals and ascorbate levels, collectively acting as pro-oxidants. Nonetheless, the CNS possesses relatively fewer antioxidant systems compared to other organs [126]. Substantial evidence underscores the roles of inflammation and oxidative stress as prominent features in AD, PD, and ALS, linking oxidative stress to neuronal death and neural dysfunction. Notably, mitochondrial dysfunction also features prominently in these diseases, likely playing a critical role in generating and amplifying reactive oxygen species (ROS), thereby contributing to the pathophysiology of these diseases [127, 128]. Numerous genes have been implicated in the onset of neurodegenerative diseases, with mutations in superoxide dismutase (SOD) genes identified in ALS patients, present in nearly 20% of familial cases.