## 7 Molecular Effects of Nanoplastics in Processes of Neurotoxicity
### Neurodegeneration
The SOD family proteins represent one of the primary lines of defense against oxidative stress in organisms, with most oxygen-reliant organisms expressing at least one SOD isoform. This family of metalloenzymes acts as antioxidants by scavenging superoxides (e.g., O\({}_{2}\)\(\bullet\)), and deleterious mutations have been shown to alter SOD activity, resulting in the accumulation of highly toxic hydroxyl radicals. Mammals possess three isoforms of SOD: cytoplasmic Cu/ZnSOD (SOD), mitochondrial MnSOD (SOD), and extracellular Cu/ZnSOD (SOD), all of which necessitate catalytic metals (Cu or Mn) for activation [129]. The consequences of NPs' interactions with proteins have been investigated and described, including protein corona formation, NPs-induced coalescence, and alterations in secondary protein structure [112]. Of particular relevance to neurotoxic and neurodegenerative processes is the interaction of plastics with the key enzyme superoxide dismutase (SOD), with recently described structural and functional consequences [130]. These authors employed PS microspheres of 70 nm (PS-NPs) and conducted binding studies on purified SOD, the Cu/Zn isoform, employing multispectroscopic approaches (UV-vis, circular dichroism, fluorescence emission spectra). Addition of PS-NPs induces peptide bond alterations in the backbone of SOD1, loosening and unfolding its structure. PS-NPs alter the secondary structure of SOD1, affecting the enzyme's percentage of \(\alpha\)-helix, \(\beta\)-sheet, \(\beta\)-turn, and random coil. Moreover, PS-NPs and SOD form new complexes, leading to larger aggregate sizes. At varying concentrations of NPs, structural alterations contribute to increased SOD1 activity [130]. The underlying hypothesis suggests that, with increased PS-NPs concentrations, aggregate sizes enlarge, loosening the skeletal structure of SOD1 and facilitating substrate entry into the enzyme's active center. However, elevated SOD activity, without a concomitant rise in catalase levels, may escalate the Fenton reaction, generating hydroxyl radicals from hydrogen peroxide, thereby heightening oxidative stress [131]. Catalase serves as a crucial enzyme in the pathway for ROS removal, converting hydrogen peroxide into water and molecular oxygen. The interaction of catalase with NPs and ensuing enzymatic activity assumes particular significance. Multispectral approaches and enzyme activation assays reveal alterations in catalase's internal structure and a corresponding decrease in enzyme activity upon exposure to polystyrene NPs [132]. These findings complement the depiction of an ROS-enriched environment devoid of key enzymes crucial for their removal, conditions intimately linked to neurodegeneration. Both NP size (20-1000 nm) and different concentrations (2-16 mg/L) can differentially impact SOD activity and structure [133]. Smaller NPs are more prone to inducing SOD coalescence and a looser SOD skeleton. With increasing NP concentrations, enhanced binding with the enzyme's metal active site is observed, resulting in reduced SOD activity. The observed effects can be summarized as NPs binding to SOD, inducing changes in the enzyme's conformational structure, ultimately affecting the activity of superoxides' removal of this pivotal enzyme. However, it is important to note that [PERSON] and collaborators [133] included and classified plastic particles of 500 and 1000 nm into the NPs, but what is relevant is that they observed major effects on SOD skeleton due to the smaller size. NPs not only interact with the three-dimensional structure of antioxidant enzymes, but also alter the polarity around tyrosine residues in SOD. In 2009, the role of a highly conserved tyrosine residue (Tyr34) on human SOD2 (MnSOD) structure and catalysis was elucidated [134]. Intriguingly, mutational studies substituting Tyr with residues possessing varying polarity (e.g., Asp, Phe, Val) substantially diminished the catalytic rate constant for superoxide reduction.