Emerging role of PANoptosis in kidney diseases: molecular mechanisms and therapeutic opportunities.

Abstract

Kidney diseases represent a significant global public health challenge, characterized by complex pathogenesis, high incidence, low awareness, insufficient early screening, and substantial treatment disparities. Effective therapeutic options remain lacking. Programmed cell death (PCD), including apoptosis, pyroptosis, and necroptosis, play pivotal roles in the pathogenesis of various kidney diseases. In 2019, PANoptosis, a novel form of inflammatory cell death, was introduced, providing new insights into innate immunity and PCD research. Although research on PANoptosis in kidney diseases is still limited, identifying key molecules within PANoptosomes and understanding their regulatory roles is critical for disease prevention and management. This review summarizes the various forms of PCD implicated in kidney diseases, along with PANoptosomes activated by Z-DNA binding protein 1 (ZBP1), absent in melanoma 2 (AIM2), receptor-interacting protein kinase 1 (RIPK1), NOD-like receptor family CARD domain containing 12 (NLRP12), and NOD-like receptor family member C5 (NLRC5). It also reviews the advancements in PANoptosis research in the field of kidney diseases, particularly in renal tumors and acute kidney injuries (AKI). The goal is to establish a foundation for future research into the role of PANoptosis in kidney diseases.