PANoptosis nexus in ischemia-reperfusion injury: from integrated cell death mechanisms to novel therapeutic opportunities

Ischemia-reperfusion injury (IRI) can activate multiple cell death pathways, leading to dysfunction of multiple organs. PANoptosis is a new inflammatory cell death form recently discovered and it is also an integrated cell death mode, which includes the features of pyroptosis, apoptosis, necroptosis. Rather than a simple addition of these routes, PANoptosis is a special type of biology process with its own regulatory mechanism and plays an important regulatory role in the occurrence of IRI. The review focuses on the concept of PANoptosis, elaborating on its molecular mechanisms and detection methods, with a particular emphasis on exploring the regulatory networks of PANoptosis in various IRI. In addition, various potential treatment strategies targeting PANoptosis analyzed in depth, including small molecule inhibitors, natural products, gene intervention, and stem cell therapy. The overall goal is to clarify the importance of PANoptosis in the pathological mechanism of IRI and to explore the possibility of using it as a focus for clinical treatment.