Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC 27710, USA.
Open Biol. 2020 Sep;10(9):200099. doi: 10.1098/rsob.200099. Epub 2020 Sep 2.
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.
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。