China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
Quimica y Farmacia, Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile.
Curr Pharm Des. 2018;24(14):1449-1484. doi: 10.2174/1381612824666180327165604.
During the past decade, an abundance of new evidence highlighted the importance of inflammation in the development of chronic pathologies such as neurodegeneration, cancer, diabetes, cardiovascular disease and inflammatory bowel disease. However, most of the current therapies do not address the underlying problem and better therapies are urgently needed. A growing number of researchers have discovered various signaling pathways that are associated with the initiation and progression of inflammation. Among different pathways, we will focus on three classical inflammatory pathways: p38 MAPK, IL-6/JAK/STAT3 and PI3K; and a non-classical inflammatory pathway, the Hippo. Recently, the Hippo pathway has been linked to various inflammatory modulators such as FoxO1/3, TNFα, IL-6, COX2, HIF-1α, AP-1, JAK and STAT. In this review, the molecular mechanisms, associated pathologies and selected drugs (both preclinical and clinical) of these signaling pathways will be summarized. Finally, limitations and potential risks of anti-inflammatory drugs will also be discussed.
在过去的十年中,大量新的证据强调了炎症在神经退行性疾病、癌症、糖尿病、心血管疾病和炎症性肠病等慢性疾病发展中的重要性。然而,大多数目前的治疗方法并没有解决根本问题,迫切需要更好的治疗方法。越来越多的研究人员发现了与炎症的发生和发展相关的各种信号通路。在不同的通路中,我们将重点关注三个经典的炎症通路:p38 MAPK、IL-6/JAK/STAT3 和 PI3K;以及一个非经典的炎症通路 Hippo。最近,Hippo 通路与各种炎症调节剂如 FoxO1/3、TNFα、IL-6、COX2、HIF-1α、AP-1、JAK 和 STAT 有关。在这篇综述中,将总结这些信号通路的分子机制、相关疾病和选定的药物(临床前和临床)。最后,还将讨论抗炎药物的局限性和潜在风险。