Evidence map›Paper›PMID 36940850›Full record

ArticleJournal of advanced research2024

Matrix metalloproteinase-9 inhibition prevents aquaporin-4 depolarization-mediated glymphatic dysfunction in Parkinson's disease.

Xiaoli Si, Shaobing Dai, Yi Fang, Jiahui Tang, Zhiyun Wang, Yaolin Li, Zhe Song, Ying Chen, Yi Liu, Guohua Zhao and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
15.0field-weighted citation impact, top 1% of its field
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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.

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  13. Reconstructing cerebral lymphatic clearance: an emerging target in the Alzheimer's disease therapeutic pipeline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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8 more citing papers are in PubMed but not listed here.

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 at 3 institutions in 1 country.

Xiaoli SiDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; Department of Neurology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University, School of Medicine, Yiwu, Zhejiang 322000, China.
Shaobing DaiDepartment of Anesthesiology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Yi FangDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Jiahui TangDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Zhiyun WangDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Yaolin LiDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Zhe SongDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Ying ChenDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Yi LiuDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China.
Guohua ZhaoDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China; Department of Neurology, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University, School of Medicine, Yiwu, Zhejiang 322000, China. Electronic address: gzhao@zju.edu.cn.
Baorong ZhangDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address: brzhang@zju.edu.cn.
Jiali PuDepartment of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, China. Electronic address: jialipu@zju.edu.cn.
Second Affiliated Hospital of Zhejiang University · CNZhejiang University · CNWomen's Hospital, School of Medicine, Zhejiang University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe glymphatic system offers a perivascular pathway for the clearance of pathological proteins and metabolites to optimize neurological functions. Glymphatic dysfunction plays a pathogenic role in Parkinson's disease (PD); however, the molecular mechanism of glymphatic dysfunction in PD remains elusive.

objectiveTo explore whether matrix metalloproteinase-9 (MMP-9)-mediated β-dystroglycan (β-DG) cleavage is involved in the regulation of aquaporin-4 (AQP4) polarity-mediated glymphatic system in PD.

methods1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and A53T mice were used in this study. The glymphatic function was evaluated using ex vivo imaging. TGN-020, an AQP4 antagonist, was administered to investigate the role of AQP4 in glymphatic dysfunction in PD. GM6001, an MMP-9 antagonist, was administered to investigate the role of the MMP-9/β-DG pathway in regulating AQP4. The expression and distribution of AQP4, MMP-9, and β-DG were assessed using western blotting, immunofluorescence, and co-immunoprecipitation. The ultrastructure of basement membrane (BM)-astrocyte endfeet was detected using transmission electron microscopy. Rotarod and open-field tests were performed to evaluate motor behavior.

resultsPerivascular influx and efflux of cerebral spinal fluid tracers were reduced in MPTP-induced PD mice with impaired AQP4 polarization. AQP4 inhibition aggravated reactive astrogliosis, glymphatic drainage restriction, and dopaminergic neuronal loss in MPTP-induced PD mice. MMP-9 and cleaved β-DG were upregulated in both MPTP-induced PD and A53T mice, with reduced polarized localization of β-DG and AQP4 to astrocyte endfeet. MMP-9 inhibition restored BM-astrocyte endfeet-AQP4 integrity and attenuated MPTP-induced metabolic perturbations and dopaminergic neuronal loss.

conclusionAQP4 depolarization contributes to glymphatic dysfunction and aggravates PD pathologies, and MMP-9-mediated β-DG cleavage regulates glymphatic function through AQP4 polarization in PD, which may provide novel insights into the pathogenesis of PD.

Indexed as

AquaporinsGlymphatic SystemParkinson DiseaseAnimalsAstrocytesDopamineMatrix Metalloproteinase 9MiceAquaporinsDopamineMatrix Metalloproteinase 9Aquaporin-4Glymphatic systemMatrix metalloproteinase-9MetabolomicsParkinson’s disease

Identifiers

PMID36940850
PMCPMC10834796
OpenAlexW4327921896

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.