Institute of Nano Science and Technology, Habitat Centre, Mohali, Punjab, India.
Institute of Nano Science and Technology, Habitat Centre, Mohali, Punjab, India.
Nanomedicine. 2020 Feb;24:102088. doi: 10.1016/j.nano.2019.102088. Epub 2019 Aug 31.
Posttranslational modification and agglomeration of α-synuclein (α-Syn), mitochondrial dysfunction, oxidative stress and loss of dopaminergic neurons are hallmark of Parkinson's disease (PD). This paper evaluates neuroprotection efficacy of nature inspired biocompatible polydopamine nanocarrier for metformin delivery (Met encapsulated PDANPs) by crossing blood brain barrier in in vitro, 3D and in vivo experimental PD models. The neuroprotective potential was arbitrated by downregulation of phospho-serine 129 (pSer129) α-Syn, with reduction in oxidative stress, prevention of apoptosis and anti-inflammatory activities. The neuroprotective mechanism proved novel interaction of epigenetic regulator EZH2 mediated ubiquitination and proteasomal degradation of aggregated pSer129 α-Syn. In summary, this study divulges the neuroprotective role of Met loaded PDANPs by reversing the neurochemical deficits by confirming an epigenetic mediated nanotherapeutic approach for the PD prevention.
α-突触核蛋白（α-Syn）的翻译后修饰和聚集、线粒体功能障碍、氧化应激和多巴胺能神经元的丧失是帕金森病（PD）的标志。本文通过在体外、3D 和体内实验性 PD 模型中穿越血脑屏障，评估了受自然启发的生物相容性聚多巴胺纳米载体用于二甲双胍递送（Met 包封的 PDANPs）的神经保护功效。通过下调磷酸化丝氨酸 129（pSer129）α-Syn，减少氧化应激、预防细胞凋亡和抗炎活性来判断神经保护潜力。神经保护机制证明了表观遗传调节剂 EZH2 介导的泛素化和聚集的 pSer129 α-Syn 的蛋白酶体降解的新相互作用。总之，这项研究通过确认一种针对 PD 预防的表观遗传介导的纳米治疗方法，通过逆转神经化学缺陷，揭示了 Met 负载的 PDANPs 的神经保护作用。
