Evidence mapPaperPMID 41574659Full record

SynthesisCNS neuroscience & therapeutics2026

Pyroptosis in Peripheral Neuropathy: From Molecular Mechanisms to Therapeutic Targeting.

Jinhuan Wei, Mingyue Liuyuan, Zhixin Ye, Xueying Wang, Xueli Zhou, Yifan Shan, Cheng He, Chunting Zhu, Chicheng Zhou, Jingyin Bao and 2 more

Abstract readSystematic Review
In one paragraph

Synthesis in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jinhuan WeiCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.ORCID 0000-0003-2887-1564
Mingyue LiuyuanCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Zhixin YeCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Xueying WangCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Xueli ZhouDepartment of Human Anatomy, Shandong Medical College, Linyi, Shandong, China.
Yifan ShanDepartment of Medical Equipment, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Cheng HeCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Chunting ZhuCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Chicheng ZhouCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Jingyin BaoCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Yonghui ZhangCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.
Gang ChenCenter for Basic Medical Research, Medical School of Nantong University, Co-Innovation Center of Neuroregeneration, Nantong, Jiangsu, China.ORCID 0000-0003-3669-5687

Funding

Nantong Municipal Science and Technology Bureau JC2023044National Natural Science Foundation of China 32271054
6 · The paper itself

Abstract

backgroundPeripheral neuropathy (PN) is a common consequence of peripheral nervous system (PNS) disorders, yet its effective treatment remains a significant clinical challenge. Pyroptosis, an inflammatory form of programmed cell death (PCD) triggered by gasdermin A-E (GSDMA-E), contributes to the pathogenesis of PN and represents a promising therapeutic target. While reviews of pyroptosis in other diseases are extensive, comprehensive reviews focusing on PN are lacking.

methodWe systematically searched PubMed, Scopus, Web of Science, and Google Scholar (1986-2025). Only original studies investigating pyroptosis in PN were included.

resultsThis review first consolidates established evidence, highlighting a context-dependent dual role of pyroptosis in PN. Its detrimental effects in chronic pain involve canonical (caspase-1/GSDMD) or noncanonical pathways (e.g., caspase-4/5/11/GSDMD, caspase-3/GSDME, caspase-8/GSDMC), often initiated by inflammasomes (e.g., NOD-like receptor family pyrin domain containing 3 [NLRP3]). Conversely, its beneficial, tumoricidal role is leveraged in neuroblastoma. Preclinically, diverse inhibitors-including NLRP3 inhibitors (e.g., MCC950), caspase-1 inhibitors (e.g., VX-765), and P2X7R antagonists (e.g., Brilliant Blue G)-alleviate pain and promote nerve repair, while pyroptosis inducers (e.g., axitinib) combat chemoresistant tumors. We then identify critical knowledge gaps and emerging frontiers. The roles of most gasdermins (GSDMA, GSDMB, GSDMC) in PN are unknown. We explore the emerging concept of PANoptosis (crosstalk among pyroptosis, apoptosis, and necroptosis) as a novel conceptual framework for PNS pathologies, where shared molecular hubs may amplify neuroinflammation. Furthermore, despite promising strategies like combination therapy and drug repurposing, a significant translational gap exists, with no current clinical trials specifically targeting pyroptosis for PN. CONCLUSION AND PERSPECTIVE: Targeting pyroptosis is a novel therapeutic avenue for PN. This review synthesizes current mechanistic understanding, evaluates preclinical therapeutic strategies, and delineates crucial future directions, including elucidating gasdermin diversity, validating PANoptosis, and bridging the translational divide, thereby accelerating their application for patients suffering from PN.

Indexed as

Peripheral Nervous System DiseasesPyroptosisAnimalsHumansMolecular Targeted Therapygasdermininflammasomemolecular mechanismsperipheral neuropathypyroptosistherapeutic targets

Identifiers

PMID41574659
PMCPMC12828674

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.