Molla Meseret Derbew, Akalu Yonas, Geto Zeleke, Dagnew Baye, Ayelign Birhanu, Shibabaw Tewodros
Department of Biochemistry, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
Department of Human Physiology, School of Medicine, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
J Inflamm Res. 2020 Oct 20;13:749-764. doi: 10.2147/JIR.S277457. eCollection 2020.
Caspase-1 is the first and extensively studied inflammatory caspase that is activated through inflammasome assembly. Inflammasome is a cytosolic formation of multiprotein complex that aimed to start inflammatory response against infections or cellular damages. The process leads to an auto-activation of caspase-1 and consequent maturation of caspase-1 target molecules such as interleukin (IL)-1β and IL-18. Recently, the role of caspase-1 and inflammasome in inflammatory-induced noncommunicable diseases (NCDs) like obesity, diabetes mellitus (DM), cardiovascular diseases (CVDs), cancers and chronic respiratory diseases have widely studied. However, their reports are distinct and even they have reported contrasting role of caspase-1 in the development and progression of NCDs. A few studies have reported that caspase-1/inflammasome assembley has a protective role in the initiation and progression of these diseases through the activation of the noncanonical caspase-1 target substrates like gasdermin-D and regulation of immune cells. Conversely, others have revealed that caspase-1 has a direct/indirect effect in the development and progression of several NCDs. Therefore, in this review, we systematically summarized the role of caspase-1 in the development and progression of NCDs, especially in obesity, DM, CVDs and cancers.
半胱天冬酶-1是首个被广泛研究的炎性半胱天冬酶，它通过炎性小体组装被激活。炎性小体是一种胞质中的多蛋白复合体结构，旨在启动针对感染或细胞损伤的炎症反应。该过程导致半胱天冬酶-1的自激活以及半胱天冬酶-1靶分子如白细胞介素（IL）-1β和IL-18的成熟。最近，半胱天冬酶-1和炎性小体在肥胖、糖尿病（DM）、心血管疾病（CVD）、癌症和慢性呼吸道疾病等炎症诱导的非传染性疾病（NCD）中的作用已得到广泛研究。然而，它们的报道各不相同，甚至在半胱天冬酶-1在非传染性疾病的发生和发展中的作用方面存在相互矛盾的报道。一些研究报告称，半胱天冬酶-1/炎性小体组装通过激活gasdermin-D等非经典半胱天冬酶-1靶底物和调节免疫细胞，在这些疾病的起始和进展中具有保护作用。相反，其他研究表明半胱天冬酶-1在几种非传染性疾病的发生和发展中具有直接/间接作用。因此，在本综述中，我们系统地总结了半胱天冬酶-1在非传染性疾病，特别是肥胖、糖尿病、心血管疾病和癌症的发生和发展中的作用。
