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Driving GDNF expression: the green and the red traffic lights.
Progress in Neurobiology ( IF 6.7 ) Pub Date : 2008-10-01 , DOI: 10.1016/j.pneurobio.2008.09.006
Ana Saavedra 1 , Graça Baltazar , Emília P Duarte
Affiliation  

Glial cell line-derived neurotrophic factor (GDNF) is widely recognized as a potent survival factor for dopaminergic neurons of the nigrostriatal pathway that degenerate in Parkinson's disease (PD). In animal models of PD, GDNF delivery to the striatum or the substantia nigra protects dopaminergic neurons against subsequent toxin-induced injury and rescues previously damaged neurons, promoting recovery of the motor function. Thus, GDNF was proposed as a potential therapy to PD aimed at slowing down, halting or reversing neurodegeneration, an issue addressed in previous reviews. However, the use of GDNF as a therapeutic agent for PD is hampered by the difficulty in delivering it to the brain. Another potential strategy is to stimulate the endogenous expression of GDNF, but in order to do that we need to understand how GDNF expression is regulated. The aim of this review is to do a comprehensive analysis of the state of the art on the control of endogenous GDNF expression in the nervous system, focusing mainly on the nigrostriatal pathway. We address the control of GDNF expression during development, in the adult brain and after injury, and how damaged neurons signal glial cells to up-regulate GDNF. Pharmacological agents or natural molecules that increase GDNF expression and show neuroprotective activity in animal models of PD are reviewed. We also provide an integrated overview of the signalling pathways linking receptors for these molecules to the induction of GDNF gene, which might also become targets for neuroprotective therapies in PD.

中文翻译:

推动GDNF表达:绿色和红色交通信号灯。

胶质细胞源性神经营养因子(GDNF)被广泛认为是黑质纹状体途径多巴胺能神经元在帕金森氏病(PD)中退化的有效存活因子。在PD的动物模型中,GDNF传递至纹状体或黑质可保护多巴胺能神经元免受随后的毒素诱导的损伤,并挽救先前受损的神经元,从而促进运动功能的恢复。因此,GDNF被提议作为一种针对PD的潜在疗法,旨在减缓,阻止或逆转神经退行性变,这是以前的综述所解决的问题。然而,GDNF作为PD的治疗剂的使用由于难以将其输送到大脑而受到阻碍。另一种可能的策略是刺激GDNF的内源性表达,但为此,我们需要了解GDNF表达是如何调控的。这篇综述的目的是对神经系统中内源性GDNF表达控制的最新技术水平进行全面分析,主要侧重于黑质纹状体途径。我们解决了发育过程中,成年大脑中和损伤后GDNF表达的控制问题,以及受损神经元如何向神经胶质细胞发出信号以上调GDNF。审查了增加GDNF表达并在PD动物模型中显示神经保护活性的药理剂或天然分子。我们还提供了将这些分子的受体连接到GDNF基因的诱导的信号通路的综合概述,GDNF基因的诱导也可能成为PD中神经保护疗法的靶标。这篇综述的目的是对神经系统中内源性GDNF表达控制的最新技术水平进行全面分析,主要侧重于黑质纹状体途径。我们解决了发育过程中,成年大脑中和损伤后GDNF表达的控制问题,以及受损神经元如何向神经胶质细胞发出信号以上调GDNF。审查了增加GDNF表达并在PD动物模型中显示神经保护活性的药理剂或天然分子。我们还提供了将这些分子的受体连接到GDNF基因的诱导的信号通路的综合概述,GDNF基因的诱导也可能成为PD中神经保护疗法的靶标。这篇综述的目的是对神经系统中内源性GDNF表达控制的最新技术水平进行全面分析,主要侧重于黑质纹状体途径。我们解决了发育过程中,成年大脑中和损伤后GDNF表达的控制问题,以及受损神经元如何向神经胶质细胞发出信号以上调GDNF。审查了增加GDNF表达并在PD动物模型中显示神经保护活性的药理剂或天然分子。我们还提供了将这些分子的受体连接到GDNF基因的诱导的信号通路的综合概述,GDNF基因的诱导也可能成为PD中神经保护疗法的靶标。我们解决了发育过程中,成年大脑中和损伤后GDNF表达的控制问题,以及受损神经元如何向神经胶质细胞发出信号以上调GDNF。审查了增加GDNF表达并在PD动物模型中显示神经保护活性的药理剂或天然分子。我们还提供了将这些分子的受体连接到GDNF基因的诱导的信号通路的综合概述,GDNF基因的诱导也可能成为PD中神经保护疗法的靶标。我们解决了发育过程中,成年大脑中和损伤后GDNF表达的控制问题,以及受损神经元如何向神经胶质细胞发出信号以上调GDNF。审查了增加GDNF表达并在PD动物模型中显示神经保护活性的药理剂或天然分子。我们还提供了将这些分子的受体连接到GDNF基因的诱导的信号通路的综合概述,GDNF基因的诱导也可能成为PD中神经保护疗法的靶标。
更新日期:2019-11-01
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