Evidence map›Paper›PMID 41267382›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Brd4 BD1 Domain Antagonism of MS436 Preserves Blood-Brain Barrier Integrity via Rnf43/β-Catenin Signaling Pathway.

Chenxiao Li, Xiaochen Zhang, Jiangwei Xia, Shuang Liu, Yushan Du, Sihan Li, Shukui Zhang, Yong Zhang, Fen Ji, Jianwei Jiao and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 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. 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

11 authors.

Chenxiao LiZhanjiang Key Laboratory of Zebrafish Model for Development and Disease, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.
Xiaochen ZhangAcademy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, 300072, China.
Jiangwei XiaDepartment of Neurology, Xuanwu Hospital Capital Medical University, National Center for Neurological Disorders, Beijing, 100053, China.
Shuang LiuJiaozuo Hospital of Traditional Chinese Medicine, Jiaozuo, 454150, China.
Yushan DuCollege of Basic Medicine, Qingdao University, Qingdao, 266071, China.
Sihan LiKey Laboratory of Organ Regeneration and Reconstruction, Chinese Academy of Science, Beijing, 100101, China.
Shukui ZhangKey Laboratory of Organ Regeneration and Reconstruction, Chinese Academy of Science, Beijing, 100101, China.
Yong ZhangNeuroscience Research Institute and Department of Neurobiology, School of Basic Medical Sciences, Peking University, Key Laboratory for Neuroscience, Ministry of Education of China and National Health Commission of the People's Republic of China, Beijing, 100083, China.
Fen JiKey Laboratory of Organ Regeneration and Reconstruction, Chinese Academy of Science, Beijing, 100101, China.
Jianwei JiaoKey Laboratory of Organ Regeneration and Reconstruction, Chinese Academy of Science, Beijing, 100101, China.
Jingjing ZhangZhanjiang Key Laboratory of Zebrafish Model for Development and Disease, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, China.ORCID https://orcid.org/0000-0002-8789-4638

Funding

High-level Talents Scientific Research Start-up Funds of the Affiliated Hospital of Guangdong Medical University 2081Z20230014High-level Talents Scientific Research Start-up Funds of the Affiliated Hospital of Guangdong Medical University 2081Z20230015National Key R&D Program of China 2024YFA1802200National Key R&D Program of China 2024YFA1802600National Natural Science Foundation of China 32222028National Natural Science Foundation of China 32230040National Natural Science Foundation of China 32450088National Natural Science Foundation of China 92368203Special Project for Clinical and Basic Sci & Tech Innovation of Guangdong Medical University GDMULCJC2024113Special Project for Clinical and Basic Sci & Tech Innovation of Guangdong Medical University GDMULCJC2025010
6 · The paper itself

Abstract

Blood-brain barrier (BBB) disruption is central to neurodegenerative and cerebrovascular diseases, but its causal role and therapeutic targeting remain challenging. Bromodomain and extraterminal domain (BET) proteins, particularly Brd4, regulate transcription via dual bromodomains (BD1, BD2). While BD1 antagonists are explored for tumors and BD2 antagonists for inflammation, their impact on cerebrovascular integrity is unclear. Crucially, opposing BBB effects of domain-specific BET antagonism: the BD2 antagonist RVX208 disrupt the BBB, whereas the BD1 antagonist MS436 significantly reduces leakage and improves neurological outcomes, revealing therapeutic potential is demonstrated. Mechanistically, endothelial Brd4 critically suppresses BBB stability. Its ablation upregulates tight junction (TJ) proteins. Brd4, acting exclusively through its BD1 domain, destabilizes TJs via Rnf43 is identified, which promotes β-catenin and TJ protein degradation. This defines a novel Brd4 BD1/Rnf43/β-catenin axis essential for BBB integrity. The findings establish Brd4 BD1 inhibition as a novel BBB-protective strategy and position MS436 for repurposing in cerebrovascular diseases, necessitating reevaluation of domain-specific BET targeting for neurovascular pathologies.

Indexed as

beta CateninBlood-Brain BarrierCell Cycle ProteinsTranscription FactorsUbiquitin-Protein LigasesAnimalsBromodomain Containing ProteinsHumansMiceNuclear ProteinsSignal TransductionTight Junctionsbeta CateninBRD4 protein, humanBrd4 protein, mouseBromodomain Containing ProteinsCell Cycle ProteinsNuclear ProteinsTranscription FactorsUbiquitin-Protein Ligasesblood‐brain barrierbromodomaincerebrovascular diseasesClaudin 5tight junction

Identifiers

PMID41267382
PMCPMC12866839

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.