Targeting panoptosis: a narrative review of its therapeutic potential in kidney disease

Area of Science:

• Nephrology
• Cell Biology
• Immunology

Background:

• Renal diseases pose a significant global health burden.
• PANoptosis, a unified programmed cell death pathway involving pyroptosis, apoptosis, and necroptosis, contributes to renal tissue damage via the PANoptosome complex.

Purpose of the Study:

• To systematically review the composition and regulatory mechanisms of PANoptosis.
• To explore the role of PANoptosis in various kidney pathologies, including acute kidney injury (AKI), chronic kidney disease (CKD), diabetic kidney disease (DKD), and renal tumors.
• To examine the interplay between PANoptosis and key cellular processes like mitochondrial dysfunction, ER stress, non-coding RNAs, ferroptosis, and autophagy.

Main Methods:

• Systematic literature review of PANoptosis.
• Analysis of preclinical studies investigating therapeutic targets.
• Examination of cellular processes and their interaction with PANoptosis.

Main Results:

• PANoptosis involves combined activation of pyroptotic, apoptotic, and necroptotic signaling.
• Preclinical studies indicate therapeutic potential in targeting PANoptosis-related molecules (e.g., ZBP1, caspase-8, NLRP3) for kidney diseases.
• Clinical application is currently limited by a lack of human data.

Conclusions:

• PANoptosis is a significant contributor to renal tissue damage and kidney pathologies.
• Targeting PANoptosis presents a promising therapeutic strategy for nephrological disorders.
• Future research must validate biomarkers, develop specific modulators, and clarify advantages over single cell death pathway inhibition.