Institute of Nano Science and Technology, Knowledge City, Sector-81, SAS Nagar, Mohali 140306, Punjab, India.
Institute of Nano Science and Technology, Knowledge City, Sector-81, SAS Nagar, Mohali 140306, Punjab, India.
Biomater Adv. 2022 Feb;133:112602. doi: 10.1016/j.msec.2021.112602. Epub 2021 Dec 24.
Parkinson's disease (PD) is the second most neurodegenerative disease caused due to synucleinopathy leads to the death of dopaminergic and serotonergic neurons. The approach to reduce synucleinopathy paves the therapeutic way in PD management. Recent studies highlight anti-Parkinsonism effect of Hytrin that regulates energy homeostasis via activation of mitochondrial redox regulator; IDH2 leading to attenuation of synucleinopathy. However, the burst release kinetics of Hytrin restricts its therapeutic potential. Therefore, we aimed to improve Hytrin release kinetics through nanocarrier mediated delivery, replenish dopamine and serotonin by formulating Hytrin loaded polydopamine serotonin nanohybrid for PD protection. Present study also explores IDH2 mediated neuroprotective action in retardation of synucleinopathy for PD prevention. Nanoformulation has shown effective neurotherapeutic potential by improving Hytrin release profile in the reduction of PD symptoms in vitro and ex vivo. The neuroprotective effect has been attributed to IDH2 induction and alpha-synuclein reduction against rotenone insults. The direct physical interaction of IDH2 and alpha-synuclein, PD hallmark has been uncovered. The study divulges that the restorative effect of our nanoformulation significantly retards the PD deficits byinducing IDH2 mediated alpha-synuclein ubiquitination and proteasomal degradation pathway.
帕金森病（PD）是第二大神经退行性疾病，由于突触核蛋白病导致多巴胺能和血清素能神经元死亡。减少突触核蛋白病的方法为 PD 管理开辟了治疗途径。最近的研究强调了 Hytrin 的抗帕金森病作用，它通过激活线粒体氧化还原调节剂 IDH2 来调节能量稳态，从而减轻突触核蛋白病。然而，Hytrin 的爆发释放动力学限制了其治疗潜力。因此，我们旨在通过纳米载体介导的递送来改善 Hytrin 的释放动力学，通过制备 Hytrin 负载的聚多巴胺-血清素纳米杂化体来补充多巴胺和血清素，以保护 PD。本研究还探讨了 IDH2 介导的神经保护作用在延缓帕金森病中的突触核蛋白病中的作用。纳米制剂通过改善 Hytrin 的释放特性，在体外和体内减少 PD 症状方面显示出有效的神经治疗潜力。神经保护作用归因于 IDH2 的诱导和 alpha-synuclein 的减少对抗鱼藤酮的损伤。已经揭示了 IDH2 和 alpha-synuclein 之间的直接物理相互作用，这是 PD 的标志。研究表明，我们的纳米制剂的恢复效果通过诱导 IDH2 介导的 alpha-synuclein 泛素化和蛋白酶体降解途径，显著延缓了 PD 缺陷。
