Dong Jie, Li Song, Mo Jing-Lin, Cai Huai-Bin, Le Wei-Dong
The Center for Translational Research on Neurological Diseases, The First Affiliated Hospital, Dalian Medical University, Dalian, China.
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
CNS Neurosci Ther. 2016 May;22(5):351-9. doi: 10.1111/cns.12536. Epub 2016 Mar 25.
Previous studies have documented that orphan nuclear receptor Nurr1 (also known as NR4A2) 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.
先前的研究已证明，孤儿核受体Nurr1（也称为NR4A2）在中脑多巴胺（DA）神经元的发育、分化和存活中发挥重要作用。此外，有报道称Nurr1缺陷与帕金森病（PD）相关。因此，Nurr1可能是PD的一个潜在治疗靶点。近期来自体外和体内研究的新证据表明，激活Nurr1的化合物和Nurr1基因疗法不仅能够增强DA神经传递，还能保护DA神经元免受环境毒素或小胶质细胞介导的神经炎症所诱导的细胞损伤。此外，与Nurr1相互作用或调节其功能的调节剂，如视黄酸X受体、环磷酸腺苷反应元件结合蛋白、胶质细胞源性神经营养因子和Wnt/β-连环蛋白通路，有可能增强基于Nurr1的疗法在PD中的效果。本综述重点介绍了基于Nurr1的疗法临床前研究的最新进展，并讨论了这种新兴疗法作为有前景的新一代PD药物的前景。
