A new perspective on the potential application of RIPK1 in the treatment of sepsis.

RIPK1 is a global cellular sensor that can determine the survival of cells. Generally, RIPK1 can induce cell apoptosis and necroptosis through TNF, Fas and lipopolysaccharide stimulation, while its scaffold function can sense the fluctuation of cellular energy and promote cell survival. Sepsis is a nonspecific disease that seriously threatens human health. There is some dispute in the literature about the role of RIPK1 in sepsis. In this review, the authors attempt to comprehensively discuss the differential results for RIPK1 in sepsis by summarizing the underlying molecular mechanism and putting forward a tentative idea as to whether RIPK1 can serve as a biomarker for the monitoring of treatment and progression in sepsis.

Sepsis is a syndrome that poses a serious threat to human life and health and is classified as a medical emergency by the WHO. RIPK1 can regulate the onset of apoptosis and necrosis in several ways and is known as a sensor of cell survival status. A series of clinical trials of RIPK1 drugs has been conducted this year and have demonstrated promising efficacy in inflammatory diseases, in particular. In this paper, the authors summarize recent studies on the function and mechanism of RIPK1 in sepsis and combine them with the progress in RIPK1 drug development to provide information for the study of RIPK1 in sepsis.

Necrostatin-1 and necroptosis inhibition: Pathophysiology and therapeutic implications.

Necrostatin-1 (Nec-1) is a RIP1-targeted inhibitor of necroptosis, a form of programmed cell death discovered and investigated in recent years. There are already many studies demonstrating the essential role of necroptosis in various diseases, including inflammatory diseases, cardiovascular diseases and neurological diseases. However, the potential of Nec-1 in diseases has not received much attention. Nec-1 is able to inhibit necroptosis signaling pathway and thus ameliorate necroptotic cell death in disease development. Recent research findings indicate that Nec-1 could be applied in several types of diseases to alleviate disease development or improve prognosis. Moreover, we predict that Nec-1 has the potential to protect against the complications of coronavirus disease 2019 (COVID-19). This review summarized the effect of Nec-1 in disease models and the underlying molecular mechanism, providing research evidence for its future application.