PANoptosis In Microglia and Neurons Following Traumatic CNS Injury: A Systematic Review of Pathological Features and Therapeutic Implications.

Authors

Zhusheng Feng, Yingnan Fan, Tianshu Du, Peipei Huang, Yuqin Ye, Junjie Li

Published in

CNS neuroscience & therapeutics. Volume 32. Issue 10. Pages e71208.

Abstract

Traumatic brain injury (TBI) and spinal cord injury (SCI) induce PANoptosis, a pro-inflammatory programmed cell death modality orchestrated by the PANoptosome. This modality integrates pyroptosis, apoptosis, and necroptosis molecular machinery and contrasts with canonical single-pathway cell death.
This systematic review (PROSPERO CRD420261383435) followed PRISMA and searched PubMed, Web of Science, and Cochrane Library. The in vivo studies confirming PANoptosis at the protein level were included; quality was assessed using CRIME-Q, and shared genes/protein interactions were analyzed via GeneCards, STRING, and Cytoscape.
Ten studies (five TBI and five SCI) were included. PANoptosis occurs in microglia and neurons, with significant crosstalk in secondary injury. Regulatory mechanisms included transcriptional regulation, inflammatory signaling, ubiquitination, energy metabolism, proteolysis, and mitophagy. Interventions comprised specific inhibitors, Chinese medicine formula granules, small molecules, siRNAs, drugs, metabolites, plasmids, and metal ions. Key sensors included ZBP1 and NLRP12, with ASC as the main adaptor; executioners included CASP1, GSDMD, CASP3/8, RIPK1/3, MLKL, and activated forms. Ischemia was the most significant disease-gene network factor.
The primary injury activates microglia and neurons, inducing PANoptosis via multiple pathways; targeting PANoptosome assembly may preserve immuno-inflammatory balance and limit secondary damage. Future research should prioritize comprehensive PANoptosome detection, standardized animal models, CNS cell interactions, novel drug delivery, and ischemia-reperfusion injury.

PMID:
42866913
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

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