P2X7 receptor as a potential therapeutic target for perinatal brain injury associated with preterm birth
1Integrated Research Center for Fetal Medicine, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD 21287, USA.
Insights
Inflammation-induced preterm birth involves Interleukin-1 beta (IL-1β) and the P2X7 receptor (P2X7R). Targeting P2X7R offers a new therapeutic strategy for preventing perinatal brain injury.
Area of Science:
- Neuroscience
- Immunology
- Obstetrics
Background:
- Preterm birth due to inflammation is a leading cause of infant mortality.
- Interleukin-1 beta (IL-1β) drives inflammation-induced preterm labor and associated complications.
- The P2X7 receptor (P2X7R) is crucial for releasing IL-1β via the NLRP3/caspase-1 pathway.
Purpose of the Study:
- To review the role of P2X7R in inflammatory signaling.
- To explore P2X7R as a therapeutic target for perinatal brain injury.
- To discuss P2X7R modulators and its function in other inflammatory conditions.
Main Methods:
- Literature review of P2X7R function in inflammation.
- Analysis of P2X7R's role in IL-1β maturation and secretion.
- Examination of P2X7R antagonists and agonists.
Main Results:
- P2X7R activation is essential for ATP-driven NLRP3 inflammasome assembly.
- P2X7R mediates the cleavage and release of IL-1β, a key inflammatory mediator.
- P2X7R's involvement in various inflammatory diseases is highlighted.
Conclusions:
- P2X7R is a critical component of the inflammatory cascade.
- Targeting P2X7R presents a promising therapeutic approach for preventing perinatal brain injury.
- Further research into P2X7R functions is vital for developing new treatments.
Abstract:
Inflammation-induced preterm birth is the leading cause of perinatal mortality and long-term sequelae in surviving children. IL-1β is a major contributor to inflammation-induced preterm labor and its sequelae. It has recently been demonstrated that the cytokine storm and its progression depend on IL-1β release into circulation and that the P2X7 receptor (P2X7R) is the key player of the ATP-driven NLRP3/caspase-1 activation, necessary for the cleavage of pro-IL-1β to its mature form as well as its subsequent secretion. Being a key component to the inflammatory cascade, P2X7R illuminates a new therapeutic avenue to halt progression of inflammation prior to perinatal brain injury. In this review, we summarize the basic role of the P2X7 receptor in the inflammatory signaling cascade and the possibility of it being used as a therapeutic target in perinatal brain injury. We discuss the antagonists and agonists of the receptor as well as its role in other inflammatory diseases, showing the importance of discovering the functions of the receptor.
