Abstract：
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.
摘要：
活性氧（ROS）的过量产生和累积的氧化应激会导致PD患者黑质致密质（SNpc）中含神经黑色素的多巴胺能神经元变性。由于其氧化还原特性，已研究了黑色素样聚多巴胺（PDA）具有一系列抗氧化酶模拟活性（包括超氧化物歧化酶（SOD）和过氧化氢酶（CAT））去除ROS的能力。谷胱甘肽过氧化物酶(GPx)对保持ROS代谢稳态,但只有少数GPx样纳米酶被研究用于体内治疗。我们知道,硒代半胱氨酸对GPx的抗氧化活性至关重要。因此，我们将PDA与硒代半胱氨酸（SeCys）共合成，以制备具有GPx样活性的纳米复合材料（PDASeCys）。结果表明，PDASeCys纳米复合材料具有与PDA相同的CAT和SOD酶活性，但比PDA具有更好的自由基清除效率和额外的GPx酶活性。在1-甲基-4-苯基-吡啶离子(MPP+)诱导的PD细胞模型中,PDASeCys能有效提高细胞内GPx水平，保护SH-SY5Y神经元细胞免受MPP+引起的氧化应激。在体内,将PDASeCys纳米复合材料注射入黑质（SN）时，可有效抑制1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的小鼠帕金森病相关症状。这种基于聚多巴胺的含有硒代半胱氨酸的纳米复合材料具有多种酶活性，包括通过一锅法合成的GPx样活性，为氧化应激诱导的PD的神经黑色素样纳米酶治疗策略提供了便利和安全性。
