Overproduction of reactive oxygen species (ROS) and cumulative
oxidative stress induce the degeneration of neuromelanin-containing
dopaminergic neurons in the substantia nigra pars compacta (SNpc)
of PD patients. Due to its redox property, melanin-like polydopamine
(PDA) has been studied for its ability to remove ROS with a series
of antioxidant enzyme mimetic activities including superoxide dismutase
(SOD) and catalase (CAT). Glutathione peroxidase (GPx) is important
for maintaining ROS metabolic homeostasis, but only a few GPx-like
nanozymes have been studied for in vivo therapy. As we know, selenocysteine
is essential for the antioxidant activity of GPx. Hence, we co-synthesized
PDA with selenocystine (SeCys) to prepare a nanocomposite (PDASeCys)
with GPx-like activity. The results showed that the PDASeCys nanocomposite
has the same CAT and SOD enzymatic activities as PDA but better free
radical scavenging efficiency and additional GPx enzymatic activity
than PDA. In the 1-methyl-4-phenyl-pyridine ion (MPP+)-induced
PD cell model, PDASeCys could increase intracellular GPx levels effectively
and protect SH-SY5Y neuronal cells from oxidative stress caused by
MPP+. In vivo, the PDASeCys nanocomposite effectively inhibited
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium (MPTP)-induced Parkinson-related
symptoms of mice when it was injected into the substantia nigra (SN).
This polydopamine-based nanocomposite containing selenocystine with
a variety of enzymatic activities including GPx-like activity synthesized
by a one-pot method provides convenience and safety in the neuromelanin-like
nanozyme-based therapeutic strategy for oxidative stress-induced PD.