# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 7 Nanzymes in the Fighting of Neurodegenerative Diseases  
The examples described above show that many nanozymes have an inherent activity similar to that of antioxidant enzymes. On this basis, they can be used for cytoprotection, believing inflammation; thus, they promise possible applications in the treatment of oxidative stress-related medical conditions, including alleviating neurodegenerative diseases. Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by misfolded accumulation of \(\alpha\)-synuclein (\(\alpha\)-syn) [170]. New evidence suggests that oxidative stress is an inevitable pathogenesis factor contributing to the prion-like spread of protein damage [171; 172]. For example, paraquat can induce oxidative stress in vivo and in vitro, significantly leading to increased spread of \(\alpha\)-syn [171; 173; 174]. Pathological \(\alpha\)-syn has been shown to increase ROS by facilitating the spread of \(\alpha\)-syn and causing severe neurodegeneration and behavioral deficits in vivo [175]. At the same time, inhibitors of the NOS-related pathway can significantly prevent \(\alpha\)-syn-induced pathogenesis [175], indicating that reducing the level of oxidative stress may be an effective means of counteracting the pathological spread of \(\alpha\)-syn in PD. Therefore, experiments on metal-based nanozymes having antioxidative action [176], consisting of platinum and copper (called bimetallic PtCu nanoalloys), showed that the nanozymes could be applied in the treatment for PD due to their antioxidative potential. It was shown that the antioxidative action of nanozymes could prevent the spread of misfolded alpha-synuclein by breaking the positive feedback loop between the accumulation of misfolded alpha-synuclein and the formation of free radicals (Figure 6). Platinum and copper were used because of their strong antioxidant properties. The antioxidant capacity of an alloy largely depends on its composition. When injected into the brain, PtCu nanoalloys acted as CAT and SOD. It was found that nanozyme reduced disease symptoms caused by misfolded alpha-synuclein, inhibited neurotoxicity, and reduced the number of free radicals in mice. Nanozyme also prevented alpha-synuclein from moving from cell to cell and from the substantia nigra to the dorsal striatum, two midbrain areas responsible for movement and cognition [176]. [PERSON] et al. designed phenylalanine-modified CuxO nanoclusters showing potential for the treatment of PD [177]. The generated CuxO nanoclusters behaved like SOD, CAT, and GPx mimics. To further explore the potential therapeutic efficacy of these nanozymes, a mouse model of [PERSON]'s disease was constructed. CuxO nanoclusters were shown to modify the levels of Allograft inflammatory factor 1 (AIF-1, b1a1), whose expression is upregulated in microglia following nerve injury central nervous system ischemia, and several other brain diseases [178]. Iba1 levels were lowered in the PD mouse model after treatment with CuxO compared to the  
Figure 6: The mechanism action of PtCu nanozyme in the treatment of PD. Reprinted from [176], with the permission of Elsevier. untreated PD mice. PD mice treated with Cu\({}_{x}\)O nanoclusters also showed significantly better spatial learning, memory, escape latency, and swim speed during the training process, indicating that Cu\({}_{x}\)O induced cognitive regeneration. Another example of a disease whose pathogenesis is associated with the overproduction of ROS is Alzheimer's disease (AD). Cellular changes show that oxidative stress precedes the appearance of the hallmark pathologies of the disease [179]. AD, one of the most common types of dementia, affects approximately 10% of the elderly (age 65 and over) [180; 181]. Accumulation of amyloid protein (A\(\beta\)) plaques and neurofibrillary tangles in the brain are the two major pathological markers of AD [182]. A\(\beta\) accumulation induced by protein misfolding has been recognized as a hallmark of neurodegenerative disease.