NF-κB signaling -: Pros and cons of altering NF-κB as a therapeutic approach
NF-κB signaling -: Pros and cons of altering NF-κB as a therapeutic approach
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DOI：
10.1196/annals.1326.009
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发表时间：
2006-01-01
期刊：
影响因子：
--
通讯作者：
Toruner, Murat
中科院分区：
文献类型：
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作者：
Egan, Laurence J.;Toruner, Murat
转录因子核因子-κ B（NF-κ B）是数百种基因表达的主要调节因子，其中许多基因在炎症和程序性细胞死亡（细胞凋亡）的调节中起重要作用。自从20世纪80年代中期发现NF-κ B以来，这种转录因子一直是深入研究的主题。在人类炎症性肠病和许多其他炎症性疾病和癌症类型中已经观察到NF-κ B的过度或不适当活化。动物功能研究揭示了NF-κ B B在更广泛的病理生理学背景下的作用。从这些研究中，NF-κ B B在不同的细胞类型中发挥独特的功能变得非常清楚。由于NF-κ B在炎症信号传导和抑制程序性细胞死亡中的重要性，许多制药公司正在开发该途径的小分子抑制剂。在这篇文章中，我们评估了阻断NF-κ B作为炎症性肠病治疗方法的相对利弊。基于主要使用遗传方法抑制NF-κ B活性的动物研究结果，我们认为在炎症性肠病中阻断NF-κ B有一定的适应症，这提供了特别的希望。
The transcription factor, nuclear factor-kappa B (NF-kappa B), is a dominant regulator of the expression of hundreds of genes, many of which play important roles in the regulation of inflammation and programmed cell death (apoptosis). Since the discovery of NF-kappa B in the mid 1980s, this transcription factor has been the subject of intense investigation. Excess or inappropriate activation of NF-kappa B has been observed in human inflammatory bowel disease and in a host of other inflammatory diseases and type of cancer. Functional studies in animals have shed light on the role of NF-kappa B in broader pathophysiological contexts. From such studies, it has become quite clear that NF-kappa B plays unique and distinct functions in different cell types. Because of the importance of NF-kappa B in signaling inflammation, and in inhibiting programmed cell death, many pharmaceutical companies are developing small-molecule inhibitors of this pathway. In this article, we evaluate the relative pros and cons of blocking NF-kappa B as a therapeutic approach for inflammatory bowel disease. On the basis of the results of studies in animals that have primarily used genetic approaches to inhibit NF-kappa B activity, we suggest that there are certain niche indications for blocking NF-kappa B in inflammatory bowel disease that offer particular promise.