Evidence mapPaperPMID 40589337Full record

ArticleCNS neuroscience & therapeutics2025

Electroacupuncture Attenuates High-Fat Diet-Exacerbated Alzheimer's Pathology by Enhancing TFEB/TFE3-Mediated Autophagic Clearance of Tau and NLRP3 Inflammasome in 3xTg Mice.

Xiaoyan Zheng, Zhihao Luo, Jialin Zheng, Chuyu Deng, Dongmin Liu, Yiming Chen, Runjin Zhou, Jihua Zou, Guozhi Huang, Qing Zeng and 2 more

Abstract read
In one paragraph

Article in CNS neuroscience & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
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

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  7. Unraveling the Effects ofInternational journal of molecular sciences · 2025
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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.

Xiaoyan ZhengSchool of Rehabilitation Sciences, Southern Medical University, Guangzhou, China.
Zhihao LuoMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Jialin ZhengMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Chuyu DengMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Dongmin LiuMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Yiming ChenMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Runjin ZhouMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Jihua ZouSchool of Rehabilitation Sciences, Southern Medical University, Guangzhou, China.ORCID 0000-0003-0129-2271
Guozhi HuangSchool of Rehabilitation Sciences, Southern Medical University, Guangzhou, China.
Qing ZengSchool of Rehabilitation Sciences, Southern Medical University, Guangzhou, China.
Chunzhi TangMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Ju-Xian SongMedical College of Acupuncture-Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.ORCID 0000-0001-7266-2060

Funding

Guangdong Basic and Applied Basic Research Foundation 2023A1515011143Guangdong Basic and Applied Basic Research Foundation 2025A1515010815Guangdong Medical Research Fundation A2024185Guangzhou Municipal Science and Technology Project 2023A04J0421National Natural Science Foundation of China 82074042National Natural Science Foundation of China 82174479National Natural Science Foundation of China 82205245National Natural Science Foundation of China 82374571
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) pathology is increasingly linked to metabolic disturbances induced by high-fat diets (HFD), with both autophagy-lysosomal pathway (ALP) dysfunction and activation of the NLRP3 inflammasome emerging as key pathological mechanisms. This study introduces a novel approach using electroacupuncture (EA) to mitigate HFD-accelerated AD pathology, focusing on the regulatory role of transcription factors TFEB and TFE3 in ALP and their potential modulation by EA.

methods3xTg-AD mice were fed either an HFD or a standard diet for 16 weeks, followed by EA treatment at the ST36 acupoint. AAV-mediated hippocampal knockdown of TFEB and TFE3 was performed using shRNA constructs. Cognitive performance was evaluated with the Morris water maze (MWM) and Y-maze tests. Molecular analyses, including immunoblotting and immunohistochemistry, were conducted to examine the impact of EA on NLRP3 inflammasome activation, ALP dynamics, and the involvement of TFEB and TFE3 in modulating these pathways within the brain.

resultsHFD feeding significantly exacerbated Tau pathology and NLRP3 inflammasome activation in 3xTg-AD mice, leading to pronounced cognitive deficits. Notably, EA-ST36 intervention reversed these pathological effects, enhancing memory function and reducing both Tau aggregation and NLRP3 inflammasome activation. Mechanistic insights revealed that EA-ST36 activated TFEB and TFE3 by modulating the MTOR/ULK1 signaling pathway, thereby enhancing autophagic clearance of NLRP3 inflammasome components and Tau aggregates.

conclusionThis study proposes EA-ST36 as a promising therapeutic strategy for counteracting HFD-induced AD pathology by activating TFEB/TFE3-driven autophagic pathways, thereby enhancing the clearance of toxic protein aggregates and inflammasome components. These findings advance our understanding of EA's molecular mechanisms in AD therapy, offering a novel, nonpharmacological approach for mitigating diet-induced exacerbation of neurodegenerative processes.

Indexed as

Alzheimer DiseaseAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDiet, High-FatElectroacupunctureInflammasomesNLR Family, Pyrin Domain-Containing 3 Proteintau ProteinsAnimalsMaleMiceMice, Inbred C57BLMice, TransgenicBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsInflammasomesMapt protein, mouseNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousetau ProteinsTcfe3 protein, mouseTcfeb protein, mouseAlzheimer's pathologyelectroacupuncturehigh‐fat dietTFEB/TFE3

Identifiers

PMID40589337
PMCPMC12209595

What Socratic holds

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LicenceCC BY
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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.