The loss of dopaminergic neurons, majorly due to synucleinopathy, is the prime cause of Parkinson’s disease (PD) progression. Like phosphorylated synuclein, nitrated synuclein also significantly contributes to Lewy body formation in the PD etiology. Therefore, an approach to reduce nitrated synuclein enlightens the way of PD treatment. Recently, hytrin has emerged as a neurotherapeutic agent that activates IDH2 in synucleinopathy alleviation. However, burst release kinetics hamper the therapeutic efficacy of hytrin. We included our reported hytrin-loaded polydopamine-serotonin nanoparticles and utilized them for the investigation of therapeutic efficacy and molecular insights of neuroprotective action in an in vivo PD model with the aim to improve the therapeutic efficacy of hytrin. The present study explored behavioral testing, immunohistochemistry, and protein expression analysis to understand the camouflaged role of IDH2 in the activation of chaperone-mediated autophagy in the reduction of nitrated synuclein. The nanoformulation exhibited a neuroprotective efficiency through improved behavioral changes against PD deficits. The neuroprotective action has been attributed to IDH2-mediated Hsc70/Lamp2a induction in the reduction of nitrated synuclein. This study revealed the hytrin nanoformulation effect in the activation of chaperone-mediated autophagy to alleviate nitrated synucleinopathy in PD treatment.

中文翻译：

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Hytrin 纳米制剂通过伴侣介导的自噬减少硝化突触核蛋白病

主要由突触核蛋白病引起的多巴胺能神经元的丧失是帕金森病（PD）进展的主要原因。与磷酸化突触核蛋白一样，硝化突触核蛋白也对 PD 病因中路易体的形成有显着贡献。因此，减少硝化突触核蛋白的方法为PD治疗提供了思路。最近，hytrin 已成为一种神经治疗剂，可激活 IDH2 以缓解突触核蛋白病。然而，爆发释放动力学阻碍了hytrin的治疗效果。我们纳入了我们报道的负载hytrin的聚多巴胺-血清素纳米颗粒，并利用它们在体内PD模型中研究治疗效果和神经保护作用的分子见解，目的是提高hytrin的治疗效果。本研究探索了行为测试、免疫组织化学和蛋白质表达分析，以了解 IDH2 在激活伴侣介导的自噬以减少硝化突触核蛋白中的伪装作用。该纳米制剂通过改善针对帕金森病缺陷的行为改变而表现出神经保护效率。神经保护作用归因于 IDH2 介导的 Hsc70/Lamp2a 诱导硝化突触核蛋白的还原。这项研究揭示了 Hytrin 纳米制剂在激活分子伴侣介导的自噬中的作用，以减轻 PD 治疗中的硝化突触核蛋白病。