Transcriptional Factor NF-κB as a Target for Therapy in Parkinson's Disease.
Transcriptional Factor NF-κB as a Target for Therapy in Parkinson's Disease.
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DOI：
10.4061/2011/216298
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Hong JS
中科院分区：
文献类型：
--
作者：
Flood PM;Qian L;Peterson LJ;Zhang F;Shi JS;Gao HM;Hong JS
帕金森病（PD）是一种以慢性炎症为特征的神经退行性疾病。核因子κB （NF-κB）是一个可诱导转录因子家族，在多种细胞和组织中表达，包括小胶质细胞、星形胶质细胞和神经元，经典的NF-κB通路在炎症过程中激活和调节炎症介质的产生中起关键作用。经典NF-κB通路的激活是通过IKK激酶复合物的活性介导的，IKK激酶复合物由IKKα、IKKβ和IKKγ亚基的异源三聚体组成。靶向NF-κB已被提出作为治疗急慢性炎症的一种方法，目前已发现IKKβ或IKKγ特异性抑制剂的使用可抑制帕金森病小鼠和灵长类动物模型中TH+ da产生神经元的神经变性。这些研究表明，通过抑制IKK复合物靶向NF-κB的经典通路可以作为治疗PD的有效方法。
Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factor κB (NF-κB) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF-κB pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF-κB pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKKα, IKKβ, and IKKγ subunits. Targeting NF-κB has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKKβ or IKKγ has now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF-κB through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD.
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