Evidence map›Paper›PMID 41315295›Full record

ArticleNPJ Parkinson's disease2025

GDNF signaling modulation by Akkermansia muciniphila ameliorates constipation-depression comorbidity in Parkinson's disease.

Chunyan Mu, Zairen Zhou, Jingyu Li, Mingyu Su, Ke Xue, Jingyuan Zhang, Shijie Shi, Ye Li, Xiaoyu Yao, Mengxue Wang and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ Parkinson's disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Mechanism and application ofFrontiers in cellular and infection microbiology · 2026
    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

17 authors.

Chunyan Mu *Department of Neurology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.
Zairen Zhou *Institute of Science and Technology for Brain-lnspired intelligence, Fudan University, Shanghai, China.
Jingyu LiDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Mingyu SuDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Ke XueDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Jingyuan ZhangDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Shijie ShiDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Ye LiDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Xiaoyu YaoDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Mengxue WangThe Second Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Wanxiang ZhangSchool of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Zhe WangDepartment of Research and Development, Wecare Probiotics Co. Ltd., Suzhou, China.
Jianguo ZhuDepartment of Research and Development, Wecare Probiotics Co. Ltd., Suzhou, China.
Shuguang FangDepartment of Research and Development, Wecare Probiotics Co. Ltd., Suzhou, China.
Wei WangDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. weiwang@xzhmu.edu.cn.
Chuanxi TangDepartment of Neurobiology, Xuzhou Key Laboratory of Neurobiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. chxtang@xzhmu.edu.cn.
Xiaoling QinDepartment of Neurology, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China. doctorqx0@126.com.

Funding

Jiangsu Training Programs of Innovation and Entrepreneurship for Undergraduates S202510313030Natural Science Research General Project of Higher Education Institutions in Jiangsu Province 25KBJ310017the Fourth Affiliated Hospital of Tongji University SY-KYQD-02701Wellcome Trust 220232
6 · The paper itself

Abstract

Constipation and depression are prevalent non-motor symptoms (NMS) of Parkinson's disease (PD) that often co-occur, yet their shared pathophysiology remains unclear. Here, we identify enteric glial cells (EGCs) as central regulators of the gut-brain axis, wherein aberrant activation of the TLR4/NEDD4/CX43 signaling axis drives sustained ATP release, impairing serotonin (5-HT) synthesis in enterochromaffin (EC) cells. This ATP-mediated purinergic toxicity provides a unifying molecular mechanism for PD-associated constipation and depression (PD-CD). Mechanistically, TLR4 activation promotes TRAF6-dependent ubiquitination and degradation of NEDD4, reducing CX43 clearance. CX43 accumulation at the plasma membrane enhances ATP release, suppressing EC-derived 5-HT and contributing to gut dysmotility and mood disturbances. Critically, glial cell-derived neurotrophic factor (GDNF) stabilizes NEDD4 via the Ret-Src pathway, restores CX43 ubiquitination, limits ATP leakage, and rescues 5-HT synthesis, alleviating constipation and depressive phenotypes in PD mice. The probiotic Akkermansia muciniphila Akk11 (Akk11) similarly induces endogenous GDNF, producing comparable protective effects. Together, these findings establish an "EGC-EC axis" model for PD-CD and highlight GDNF-centered interventions as a promising multi-target strategy for PD NMS.

Identifiers

PMID41315295
PMCPMC12663421

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.