Evidence mapPaperPMID 41915334Full record

ReviewMolecular neurobiology2026

The Multifaceted Roles of GPR120 in Central Nervous System Disorders: Mechanistic Insights and Therapeutic Implications.

Liangxue Zhang, Honglin Jia, Chengyu Pan, Zucai Xu, Shuang Liu

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In one paragraph

Review in Molecular neurobiology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

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0 citing papers in PubMed.

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4 · The record

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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

5 authors.

Liangxue Zhang *Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Honglin Jia *Department of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Chengyu PanDepartment of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Zucai XuDepartment of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China. docxzc@126.com.
Shuang LiuDepartment of Neurology, Affiliated Hospital of Zunyi Medical University, Zunyi, China. liushuang6612@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

G protein-coupled receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), is a receptor for ω-3 polyunsaturated fatty acids (ω-3 PUFAs), mainly including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). It is widely expressed in the central nervous system on microglia, astrocytes, and neurons, where it regulates neuroinflammation and homeostasis. This review summarizes the mechanism insights and therapeutic potential of GPR120 in neurological and psychiatric disorders. Mechanistic studies indicated that GPR120 activation predominantly engages a β-arrestin2-dependent signaling pathway, which inhibits the TAK1/TAB1 complex, suppresses NF-κB and NLRP3 inflammasome pathways, and thus alleviates neuroinflammation. GPR120 signaling also regulates mitophagy and mitigates endoplasmic reticulum stress, promoting neuronal survival and function. In disease models, GPR120 activation is consistently neuroprotective, reducing seizure severity in epilepsy by inhibiting the NLRP3/caspase-1/IL-1β axis, decreasing pathological deposits in Alzheimer's disease by enhancing Aβ clearance, improving post-ischemic outcomes in stroke via anti-apoptotic and anti-inflammatory mechanisms, and improving behavior in depression models by suppressing microglial M1 polarization and restoring synaptic plasticity. Preclinical studies support the efficacy of selective GPR120 agonists (such as TUG-891, CpdA). However, clinical translation faces major challenges: differences in receptor pharmacology between humans and mice (about 82% sequence homology), weak endogenous ligands, high plasma protein binding (> 99%), and the absence of neurologically focused clinical trials. Future research should focus on addressing species differences, optimizing brain-targeted delivery strategies, and advancing translational studies from preclinical to clinical settings to evaluate the practical application value of GPR120 in central nervous system disorders.

Indexed as

Central Nervous System DiseasesReceptors, G-Protein-CoupledAnimalsHumansSignal TransductionFFAR4 protein, humanReceptors, G-Protein-CoupledCerebrovascular diseaseEpilepsyGPR120NeuroinflammationNLRP3 inflammasomeTherapeutic target

Identifiers

PMID41915334

What Socratic 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 Socratic graph.