Evidence map›Paper›PMID 40736565›Full record

ArticleCellular and molecular life sciences : CMLS2025

STAT1 and STAT6 orchestrate Cbs transcription and transsulfur metabolism in microglia and contribute to parkinson's disease-related neuroinflammation.

Yang Liu, Zhen Wang, Ya-Ting Ma, Yu-Xuan Chen, Xin-Yi Qian, Xiao-Ou Hou, Bo Wan, Hai-Gang Ren, Li-Fang Hu

Abstract read
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In one paragraph

Article in Cellular and molecular life sciences : CMLS, 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

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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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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

9 authors.

Yang Liu *Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
Zhen Wang *Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
Ya-Ting MaJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, Jiangsu, China.
Yu-Xuan ChenJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, Jiangsu, China.
Xin-Yi QianDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
Xiao-Ou HouDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
Bo WanDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China.
Hai-Gang RenJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China.
Li-Fang HuDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China. hulifang@suda.edu.cn.ORCID http://orcid.org/0000-0001-8326-7779

Funding

Discipline Construction Program of the Second Affiliated Hospital of Soochow University XKTJTD202004Key Project of the Natural Science Foundation of Jiangsu Provincial Higher Education Institutions 21KJA180003National Natural Science Foundation of China 82104190National Natural Science Foundation of China 82171251, 81870997Priority Academic Program Development of Jiangsu Higher Education Institutions Priority Academic Program Development of Jiangsu Higher Education InstitutionsResearch Center of Neurological Disease fund project of the Second Affiliated Hospital of Soochow University ND2024B01Suzhou Key Laboratory of Geriatric Neurological Disorders SZ2024001
6 · The paper itself

Abstract

Microglia-mediated neuroinflammation is implicated in the pathogenesis of Parkinson’s disease (PD). Cystathionine β-synthase (CBS) and transsulfur metabolism modulate neuroinflammation. However, the regulation of Cbs transcription is poorly understood, and it remains unknown whether microglial CBS expression is affected by genetic factors in PD. Here, our in vitro study revealed that microglial CBS expression was downregulated by lipopolysaccharide (LPS)/interferon-γ (IFN-γ) but upregulated by interleukin (IL)-4/IL-13 stimulation. CBS and transsulfur metabolism not only inhibited inflammation but also promoted the anti-inflammatory transition of microglia. The mice with conditional microglial Cbs overexpression conferred resistance to LPS-induced neuroinflammation and dopaminergic neuron damage. A novel regulatory effect of the signal transducer and activator of transcription (STAT) family on Cbs transcription was identified: STAT1 as a suppressor, whereas STAT6 as an enhancer of Cbs transcription. PD-related gene DJ-1 knockdown (KD) decreased Cbs transcription through STAT1 activation in microglia. Moreover, Cbs overexpression alleviated the susceptibility of DJ-1 KD microglia to α-synuclein preformed fibrils (α-Syn PFFs) stimulation and the neurotoxicity to dopaminergic cells. Taken together, our findings reveal novel and opposite regulatory effects of STAT1 and STAT6 on microglial Cbs transcription in response to pro- and anti-inflammatory stimulation and demonstrate that CBS acts downstream of DJ-1, highlighting its role in PD.

Indexed as

Cystathionine beta-SynthaseMicrogliaNeuroinflammatory DiseasesParkinson DiseaseSTAT1 Transcription FactorSTAT6 Transcription Factoralpha-SynucleinAnimalsDopaminergic NeuronsInterferon-gammaLipopolysaccharidesMaleMiceMice, Inbred C57BLProtein Deglycase DJ-1Transcription, Geneticalpha-SynucleinCystathionine beta-SynthaseInterferon-gammaLipopolysaccharidesPARK7 protein, mouseProtein Deglycase DJ-1Stat1 protein, mouseSTAT1 Transcription FactorStat6 protein, mouseSTAT6 Transcription FactorCBSDJ-1MicrogliaSTAT1STAT6Transsulfur metabolism

Identifiers

PMID40736565
PMCPMC12311091

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LicenceCC BY-NC-ND
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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 OpenQuestion graph.