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TAK1:一种强效的肿瘤坏死因子抑制剂,用于治疗炎症性疾病。

TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases.

机构信息

Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.

出版信息

Open Biol. 2020 Sep;10(9):200099. doi: 10.1098/rsob.200099. Epub 2020 Sep 2.

Abstract

Aberrant tumour necrosis factor (TNF) signalling is a hallmark of many inflammatory diseases including rheumatoid arthritis (RA), irritable bowel disease and lupus. Maladaptive TNF signalling can lead to hyper active downstream nuclear factor (NF)-κβ signalling in turn amplifying a cell's inflammatory response and exacerbating disease. Within the TNF intracellular inflammatory signalling cascade, transforming growth factor-β-activated kinase 1 (TAK1) has been shown to play a critical role in mediating signal transduction and downstream NF-κβ activation. Owing to its role in TNF inflammatory signalling, TAK1 has become a potential therapeutic target for the treatment of inflammatory diseases such as RA. This review highlights the current development of targeting the TNF-TAK1 signalling axis as a novel therapeutic strategy for the treatment of inflammatory diseases.

摘要

异常的肿瘤坏死因子 (TNF) 信号是许多炎症性疾病的标志,包括类风湿关节炎 (RA)、肠易激综合征和狼疮。适应性 TNF 信号会导致下游核因子 (NF)-κβ信号过度活跃,从而放大细胞的炎症反应并加重疾病。在 TNF 细胞内炎症信号级联中,转化生长因子-β激活激酶 1 (TAK1) 已被证明在介导信号转导和下游 NF-κβ激活中发挥关键作用。由于其在 TNF 炎症信号中的作用,TAK1 已成为治疗炎症性疾病(如 RA)的潜在治疗靶点。本文综述了靶向 TNF-TAK1 信号轴作为治疗炎症性疾病的新治疗策略的最新进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2000/7536066/f659f20eebe8/rsob-10-200099-g1.jpg

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