Roberti Annabell, Chaffey Laura Elizabeth, Greaves David R
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Biology (Basel). 2022 Feb 26;11(3):372. doi: 10.3390/biology11030372.
NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and have proven to be controversial. Drug repurposing strategies are a promising alternative to de novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs.
核因子κB(NF-κB)是炎症、对DNA损伤的反应以及氧化应激的核心介质。由于其在众多重要细胞过程中发挥核心作用,NF-κB失调与多种重大人类疾病的病理过程相关。在包括类风湿性关节炎(RA)和多发性硬化症(MS)等疾病中,NF-κB激活会引发不适当的炎症反应。因此,作为治疗慢性炎症性疾病、自身免疫性疾病和癌症的一种方法,对NF-κB信号传导的调节正在被广泛研究。2019年末新型冠状病毒肺炎(COVID-19)的出现、随后的大流行以及感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)肺炎患者面临的巨大临床负担,促使众多医疗系统竞相重新利用现有药物来治疗肺部炎症。这些努力仍在继续,且已被证明存在争议。药物重新利用策略是一种有前景的替代全新药物研发的方法,因为它们能最大限度地缩短药物研发时间,并降低因意外副作用导致失败的风险。人们已采用不同的实验方法来确定可重新用作抗炎药物的、能抑制NF-κB的现有药物。