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Nurr1‐Based Therapies for Parkinson's Disease

机译:基于Nurr1的帕金森氏病疗法

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Summary Previous studies have documented that orphan nuclear receptor Nurr1 (also known as NR 4A2) plays important roles in the midbrain dopamine ( DA ) neuron development, differentiation, and survival. Furthermore, it has been reported that the defects in Nurr1 are associated with Parkinson's disease ( PD ). Thus, Nurr1 might be a potential therapeutic target for PD . Emerging evidence from in vitro and in vivo studies has recently demonstrated that Nurr1‐activating compounds and Nurr1 gene therapy are able not only to enhance DA neurotransmission but also to protect DA neurons from cell injury induced by environmental toxin or microglia‐mediated neuroinflammation. Moreover, modulators that interact with Nurr1 or regulate its function, such as retinoid X receptor, cyclic AMP ‐responsive element‐binding protein, glial cell line‐derived neurotrophic factor, and Wnt/ β ‐catenin pathway, have the potential to enhance the effects of Nurr1‐based therapies in PD . This review highlights the recent progress in preclinical studies of Nurr1‐based therapies and discusses the outlook of this emerging therapy as a promising new generation of PD medication.
机译:总结以前的研究已经证明,孤儿核受体Nurr1(也称为NR 4A2)在中脑多巴胺(DA)神经元的发育,分化和存活中起着重要作用。此外,据报道,Nurr1的缺陷与帕金森氏病(PD)有关。因此,Nurr1可能是PD的潜在治疗靶标。近期来自体内和体外研究的新证据表明,激活Nurr1的化合物和Nurr1基因疗法不仅能够增强DA神经传递,而且能够保护DA神经元免受环境毒素或小胶质细胞介导的神经炎症引起的细胞损伤。此外,与Nurr1相互作用或调节其功能的调节剂,如类维生素A X受体,环状AMP响应元件结合蛋白,神经胶质细胞系衍生的神经营养因子和Wnt /β-catenin途径,有可能增强这种作用。 PD中基于Nurr1的疗法的研究。这篇综述重点介绍了基于Nurr1疗法的临床前研究的最新进展,并讨论了这种新兴疗法作为有前途的新一代PD药物的前景。

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