Evidence map›Paper›PMID 40915963›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2025

The GPR120 agonist TUG-891 mitigates ischemic brain injury by attenuating endoplasmic reticulum stress and apoptosis via the PI3K/AKT signaling pathway.

Panxi Sun, Lili Wei, Xue Qin, Jia Luo, Dongsheng Fan, Yong Chen

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2025. 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

6 authors.

Panxi SunDepartment of Neurology, Peking University Third Hospital, Beijing, 100191, China; Ministry-of-Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, Shihezi, 832000, China.
Lili WeiMinistry-of-Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, Shihezi, 832000, China.
Xue QinMinistry-of-Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, Shihezi, 832000, China.
Jia LuoMinistry-of-Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, School of Medicine, Shihezi University, Shihezi, 832000, China.
Dongsheng FanDepartment of Neurology, Peking University Third Hospital, Beijing, 100191, China; Beijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, 100191, China; Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, 100191, China. Electronic address: dsfan@sina.com.
Yong ChenDepartment of Neurology, Peking University Third Hospital, Beijing, 100191, China; Beijing Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases, Beijing, 100191, China; Key Laboratory for Neuroscience, National Health Commission/Ministry of Education, Peking University, Beijing, 100191, China. Electronic address: ronaldchen@bjmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Extensive research has confirmed that omega-3 fatty acids provide cardiovascular protection primarily by activating the G protein-coupled receptor 120 (GPR120) signaling pathway. However, natural activators of this receptor often lack sufficient strength and precision. TUG-891, a recently synthesized selective GPR120 activator, has displayed significant therapeutic potential in multiple disease. This investigation seeks to evaluate the neuroprotective effects of TUG-891 against ischemic cerebral injury. To this end, an in vivo murine model of distal middle cerebral artery occlusion (dMCAO) was employed, alongside an in vitro model utilizing oxygen-glucose deprivation/reperfusion in HT22 ​cells. The results indicated that TUG-891 significantly enhanced neurological function, reduced the volume of cerebral infarction, and alleviated pathological damage following dMCAO. Moreover, TUG-891 demonstrated a significant reduction in oxidative stress levels, a decrease of markers related to endoplasmic reticulum (ER) stress, and the modulation of critical apoptotic regulators, thereby inhibiting apoptosis in both in vivo and in vitro settings. Additionally, TUG-891 was found to affect the PI3K/Akt signaling pathway, with the application of the inhibitor LY294002 negating the protective effects of TUG-891 in vitro. This comprehensive study reveals TUG-891's therapeutic potential for ischemic stroke through multi-target mechanisms involving oxidative stress mitigation, ER stress regulation, and survival pathway activation. The consistent neuroprotection observed across biological models underscores its translational value for further clinical development.

Indexed as

ApoptosisBiphenyl CompoundsBrain IschemiaEndoplasmic Reticulum StressNeuroprotective AgentsReceptors, G-Protein-CoupledAnimalsInfarction, Middle Cerebral ArteryMaleMiceMice, Inbred C57BLPhenylpropionatesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal Transduction3-(4-((4-fluoro-4'-methyl-(1,1'-biphenyl)-2-yl)methoxy)phenyl)propanoic acidBiphenyl CompoundsFFAR4 protein, mouseNeuroprotective AgentsPhenylpropionatesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReceptors, G-Protein-CoupledApoptosisEndoplasmic reticulum stressGPR120Ischemic strokePI3K/AKT signaling pathwayTUG-891

Identifiers

PMID40915963
PMCPMC12664497

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.