Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the striatum and substantia nigra (SN), which currently lacks effective therapeutic interventions. Polydopamine nanoparticles (PDA NPs), which are self-assembled from dopamine, have shown significant potential in the field of neuroscience. This study explored the effects and mechanisms of self-assembled PDA NPs in an MPTP-induced PD mice model. It was observed that mice treated with PDA NPs demonstrated notable improvements in PD motor symptoms. Moreover, PDA NPs reduced the abnormal accumulation of α-synuclein (α-Syn) and increased the expression of tyrosine hydroxylase (TH) in both the striatum and SN. Regarding the neuroprotective mechanism, PDA NPs were found to reduce the iron deposition and Fe2+ level in the striatum and SN by modulating the levels of iron transport proteins TF, TFR, and FPN1, thereby attenuating lipid peroxidation caused by Fe2+ homeostasis imbalance. Furthermore, PDA NPs upregulated the expression of antioxidant enzyme GPX4, which further diminished cellular lipid peroxidation and provided a protective effect on dopaminergic neurons. These findings suggested that PDA NPs might play a neuroprotective role by inhibiting ferroptosis in the striatum and SN in the PD mice model, which indicated that PDA NPs are promising agents for treating PD.
Xu et al. (Thu,) studied this question.