Inflammopharmacology ( IF 4.6 ) Pub Date : 2021-08-09 , DOI: 10.1007/s10787-021-00860-5 Ekta Singh 1 , Gurubasavaraja Swamy Purawarga Matada 1 , Nahid Abbas 1 , Prasad Sanjay Dhiwar 1 , Abhishek Ghara 1 , Arka Das 1
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The natural pathway of antioxidant production is mediated through Kelch-like erythroid cell-derived protein with Cap and collar homology [ECH]-associated protein 1 (Keap1)-Nuclear factor erythroid 2-related factor 2 (Nrf2) system. Keap1 maintains a low level of Nrf2 by holding it in its protein complex. Also, Keap1 facilitates the degradation of Nrf2 by ubiquitination. In other words, Keap1 is a down-regulator of Nrf2. To boost the production of biological antioxidants, Keap1 has to be inhibited and Nrf2 has to be released. Liberated Nrf2 is in an unbound state, so it travels to the nucleus to stimulate the antioxidant response element (ARE) present on the antioxidant genes. AREs activate biosynthesis of biological antioxidants through genes responsible for the production of antioxidants. In some cases of coronavirus disease 2019 (COVID-19), there is an enormous release of cytokines. The antioxidant defense mechanism in the body helps in counteracting symptoms induced by the cytokine storm in COVID-19. So, boosting the production of antioxidants is highly desirable in such a condition. In this review article, we have compiled the role of Keap1-Nrf2 system in antioxidant production. We further propose its potential therapeutic use in managing cytokine storm in COVID-19.
Graphic abstract
中文翻译：
Keap1-Nrf2 系统对 COVID-19 诱导的细胞因子风暴的管理：回顾
抗氧化剂产生的自然途径是通过具有 Cap 和衣领同源性 [ECH] 相关蛋白 1 (Keap1)-核因子红细胞 2 相关因子 2 (Nrf2) 系统的 Kelch 样红细胞衍生蛋白介导的。Keap1 通过将 Nrf2 保持在其蛋白质复合物中来维持低水平的 Nrf2。此外，Keap1 通过泛素化促进 Nrf2 的降解。换言之，Keap1 是 Nrf2 的下调因子。为了促进生物抗氧化剂的产生，必须抑制 Keap1 并释放 Nrf2。释放的 Nrf2 处于未结合状态，因此它会进入细胞核以刺激抗氧化基因上存在的抗氧化反应元件 (ARE)。ARE通过负责产生抗氧化剂的基因激活生物抗氧化剂的生物合成。在某些 2019 年冠状病毒病 (COVID-19) 病例中，细胞因子大量释放。体内的抗氧化防御机制有助于抵消 COVID-19 中细胞因子风暴引起的症状。因此，在这种情况下，非常需要促进抗氧化剂的产生。在这篇评论文章中，我们汇总了 Keap1-Nrf2 系统在抗氧化剂生产中的作用。我们进一步提出了其在管理 COVID-19 细胞因子风暴中的潜在治疗用途。
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