The molecular mechanisms and therapeutic implications of PANoptosis in ischemic diseases.

The singular forms of programmed cell death (PCD), including pyroptosis, apoptosis, and necroptosis, are inadequate for comprehensively elucidating the complex pathological mechanisms underlying ischemic diseases. PANoptosis is a unique lytic, innate immune, and inflammatory cell death pathway, initiated by innate immune sensors and driven by caspases and RIPKs through PANoptosome complexes. In diseases like cerebral ischemia, retinal ischemia, myocardial ischemia, renal ischemia, and spinal cord ischemia, targeting key regulatory factors of PANoptosis can help mitigate tissue damage. Therefore, the therapeutic potential of PANoptosis in ischemic diseases-from molecular mechanisms to clinical applications-merits further investigation. However, effectively regulating PANoptosis to achieve therapeutic outcomes remains a critical scientific challenge that must be addressed. This review focuses on the molecular mechanisms of PANoptosis in ischemic diseases and its potential therapeutic implications, aiming to provide new insights and a theoretical foundation for precision treatment in these conditions.