Evidence map›Paper›PMID 42173845›Full record

ArticleCell death & disease2026

Targeting MEF2A suppresses microglial hyperactivation and synaptic phagocytosis to attenuate epilepsy pathogenesis.

Jingheng Wu, Jiayuanyuan Fu, Shuai Wang, Yuzhang Wu, Xu Wang, Shangang Feng, Qi Shi, Yuhao Wang, Yetong Shi, Yehong Fang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

16 authors.

Jingheng WuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.ORCID http://orcid.org/0009-0004-3928-1898
Jiayuanyuan FuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Shuai WangDepartment of Functional Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
Yuzhang WuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Xu WangHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Shangang FengHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Qi ShiHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yuhao WangHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yetong ShiHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yehong FangHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Yu LanHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Qiaoli WuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Chuan DuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China.
Shaoya YinHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China. yinsya@hotmail.com.ORCID http://orcid.org/0009-0004-8080-8639
Lixia XuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China. xu_lixia@163.com.ORCID http://orcid.org/0000-0002-1843-0127
Hua YanHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, China. yanh2023@tmu.edu.cn.ORCID http://orcid.org/0000-0003-3482-0261

Funding

Tianjin Municipal Education Commission 2024ZD049, 2024ZD050
6 · The paper itself

Abstract

Microglia's role in epilepsy through neuroimmune communication is poorly understood. Mechanisms by which neurons activate microglia and how microglia affect neuronal activity to drive seizure-related inflammation remain unclear. Here, we elucidated a crucial axis connecting pathological adenosine triphosphate (ATP) release induced by epileptiform neuronal activity to microglial MEF2A-dependent hyperactivation, which exacerbates epilepsy pathology. In epilepsy models, seizures cause excessive ATP release, activating microglial P2X7 receptors, causing CAMKII phosphorylation. This triggers HDAC5 translocation, freeing MEF2A for acetylation, and enhancing transcription. Acetylated MEF2A increases CD74 and NEK7 expressions, enhancing NLRP3 inflammasome activation and microglial hyperactivation, worsening neuronal hyperexcitability by increasing inhibitory synapses clearance. Targeting microglial MEF2A with parecoxib or AAV knockdown reduced seizure severity and cognitive deficits and maintained synaptic inhibition by reducing excessive microglial phagocytosis. This reveals an ATP-P2X7-Ca

Indexed as

EpilepsyMEF2 Transcription FactorsMicrogliaPhagocytosisSynapsesAdenosine TriphosphateAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2HumansMaleMiceMice, Inbred C57BLNeuronsPhosphorylationReceptors, Purinergic P2X7Signal TransductionAdenosine TriphosphateCalcium-Calmodulin-Dependent Protein Kinase Type 2MEF2 Transcription FactorsReceptors, Purinergic P2X7

Identifiers

PMID42173845
PMCPMC13377041

What OpenQuestion holds

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Registered trials

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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 OpenQuestion graph.