# Metal Nanozymes: New Horizons in Cellular Homeostasis Regulation
## 7 Nanzymes in the Fighting of Neurodegenerative Diseases
Moreover, A\(\beta\)-induced mitochondrial dysfunction is also considered a possible AD caused through abnormal ROS expression [183]. Since ROS-induced mitochondrial dysfunction occurs earlier than A\(\beta\) plaque formation in the brain, protecting the mitochondria from oxidative damage would be useful in the prevention and early treatment of AD. Recently, [PERSON] et al. designed CeO\({}_{2}\) nanoparticle modified with triphenylphosphonyl (TPP) as a new platform for the treatment of AD [184]. The resulting nanocomposite favored being localized to the mitochondria, markedly inhibiting A\(\beta\)-induced mitochondrial ROS and inhibiting neuronal death in the 5 XFAD AD transgenic mouse model. In a mouse model, TPP-modified CeO\({}_{2}\) nanoparticles attenuated A\(\beta\)-Induced neuronal cell damage. This can be used as a new mitochondrial therapy for neuroinflammation, which is of great importance in the treatment of Alzheimer's disease and other neurodegenerative diseases. [PERSON] et al. [185] designed ceria/polyoxometalate hybrid nanomaterials (CeONP@POMs) nanoparticles. As mimics of proteolytic enzymes. These nanozymes were shown to effectively inhibit A\(\beta\) aggregation as well as reduce intracellular ROS levels. CeONP@POM was found to promote the proliferation of PC12 pheochromocytoma of the rat adrenal medulla cells, while effectively inhibiting the A\(\beta\)-induced activation of BV2 microglial cells. An earlier study found that POMs, especially characterized with Wells-Dawson structure, inhibited the aggregation of A\(\beta\) by binding to the His13 to Lys16 (HHQK) cationic region [186]. [PERSON] et al. [187] studied the antioxidant effects in vitro and in vivo of the Fe\({}_{3}\)O\({}_{4}\) nanoparticles. Two cell lines were used in their work in vitro tests, including PC12, rat adrenal medullary phaochromocytoma from the fetal nerve crest. NPs were shown to locate in cytosol. Fe\({}_{3}\)O\({}_{4}\) NPs with CAT-like properties can efficiently remove intracellular excess ROS in this neutral environment, protecting cells from oxidative damage and H\({}_{2}\)O\({}_{2}\)-induced apoptosis. The neuroprotective properties of Fe\({}_{3}\)O\({}_{4}\) nanoparticles were tested in vitro on PC12 cells. PC12 cells originate from the neural crest that has a mixture of neuroplastic cells and eosinophilic cells and can differentiate into neuron-like cells by nerve growth factor (NGF) stimulation. 1-methyl-4-phenylpyridinium ion (MPP+) induces oxidative stress and apoptosis in differentiated PC12 cells, which is often used as a model for neuroprotective assays relevant to PD. Cellular studies showed that NP Fe\({}_{3}\)O\({}_{4}\) can be effective in ameliorating cell death induced by 1-methyl-4-phenylpyridinium (MPP+) as well as reducing the levels of \(\alpha\)-synuclein activation protein and caspase-3. The authors investigated the function of NPs also in AD. They applied a classic in vivo model based on ectopic expression of A\(\beta\) in _Drosophila_[188]. For the fly AD model, neuronal-specific expression of A\(\beta\) peptide was achieved by crossing the _elav_-Gal4 and UAS-A\(\beta\) lines, allowing tissue-specific expression of A\(\beta\) throughout the nervous system. When fed with food containing Fe\({}_{3}\)O\({}_{4}\) NP, AD-model fruit flies showed increased climbing ability and longer lifespan as compared to untreated ones. The Drosophila AD model further verified the excellent antioxidant properties of NP Fe\({}_{3}\)O\({}_{4}\) in delaying animal aging and ameliorating ROS-induced neurodegeneration. It is widely known that high concentrations of metal ions (such as Cu\({}^{2+}\) and Zn\({}^{2+}\)) play an important role in the accumulation of A\(\beta\) deposition and its neurotoxicity [189; 190; 191]. Therefore, in addition to oxidative damage, metal ion abnormalities can also be used as targets in AD therapy [26]. Having this in mind, [PERSON] et al. [125] used the discussedabove multimodal G-CeO\({}_{2}\)NPs nanoparticles to prevent A\(\beta\) aggregation.