Evidence map›Paper›PMID 42263400›Full record

ArticleEBioMedicine2026

The complement C3-microglial axis in depression of Parkinson's disease: from mechanism to therapeutic intervention.

Qiao Yin, Mengyang Ding, Yurui Tang, Yuwan Qi, Yuan Qin, Hong Jin, Yang Li, Jili Bao, Shuyang Ma, Ying Li and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

23 authors.

Qiao YinDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Mengyang DingInstitute of Molecular Enzymology, School of Life Sciences, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Yurui TangInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 201203, China.
Yuwan QiJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
Yuan QinJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, China.
Hong JinDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Yang LiDepartment of Neurology, Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical University, Huzhou, 313000, China.
Jili BaoDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Shuyang MaDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Ying LiDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Haozhe DingInstitute of Molecular Enzymology, School of Life Sciences, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Xinyu AnInstitute of Molecular Enzymology, School of Life Sciences, Suzhou Medical College, Soochow University, Suzhou, 215123, China.
Enyou QiaoDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Yan TangDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Qilin ZhangDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China.
Linna WangLanzhou Biotechnique Development Co., Ltd., Lanzhou, Gansu, 730000, China.
Jianfeng ShaoDepartment of Neurology, The Third People's Hospital of Zhangjiagang City, Suzhou, 215600, Jiangsu, China.
Jianfeng FengInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 201203, China.
Li-Fang HuJiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, China. Electronic address: hulifang@suda.edu.cn.
Jing WangInstitute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, 201203, China. Electronic address: wangjing_@fudan.edu.cn.
Pan FangInstitute of Molecular Enzymology, School of Life Sciences, Suzhou Medical College, Soochow University, Suzhou, 215123, China; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032, China. Electronic address: panfang@sioc.ac.cn.
Weifeng LuoDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China. Electronic address: lwfwxx@126.com.
Qifei CongDepartment of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, Institute of Neuroscience, Soochow University, Suzhou, 215123, China; Biomedical Basic Research Center (BBRC) of Jiangsu, Soochow University, Suzhou, 215123, China; Department of Nephrology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China; Institute of Neurological Diseases, Soochow University-Suzhou Blue Cross Brain Hospital, Soochow University, Suzhou, 215123, China; School of Life Sciences, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Soochow University, Suzhou, 215123, China. Electronic address: qfcong@suda.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDepression is a common and early non-motor symptom of Parkinson's disease (PD) with significant sexual dimorphism, yet its underlying molecular mechanisms remain poorly understood. This study aimed to elucidate the sex-specific plasma proteomic profiles of depression in patients with PD (DPD) and to investigate the role of complement-mediated synaptic pruning in its pathophysiology.

methodsPlasma proteomic analysis was performed on data from the Parkinson's Progression Markers Initiative (PPMI) and an independent validation cohort, stratified by sex. Functional enrichment analyses identified dysregulated pathways. A chronic MPTP/probenecid-induced mouse model of PD was used to validate findings. Behavioural tests assessed motor and depressive-like phenotypes. Proteomic, biochemical, and imaging techniques were used to evaluate protein expression, synapse density, and microglial phagocytosis. The therapeutic mechanism of Botulinum Neurotoxin A (BoNT/A) on DPD was investigated in wild-type, C3

findingsProteomic profiling revealed both conserved complement-driven immune dysfunction and profound sex-divergent molecular perturbations underlying PD and DPD. Complement and coagulation cascades were consistently upregulated in both sexes. In MPTP-treated male and female mice, hippocampal complement components (C1Q, C3, C3aR) and downstream signalling (p-STAT3, p-P65) were elevated, accompanied by microglial synapse phagocytosis and depressive-like behaviours. Genetic deletion of C3 rescued both MPTP-induced motor and depressive-like behavioural deficits and prevented hippocampal synaptic loss associated with microglial synaptic engulfment. BoNT/A treatment alleviated depressive-like behaviours and reduced microglial synaptic engulfment in an MPTP model; these therapeutic effects were abolished in C3

interpretationDPD exhibits distinct sex-specific immune signatures, with convergent complement pathway activation driving microglial synaptic pruning and depressive symptoms. The antidepressant effect of BoNT/A is mediated through inhibition of the C3-C3aR signalling axis. These findings highlight the potential for sex-stratified diagnostics and complement-targeted therapies for depression in patients with PD. A key limitation is that our clinical analyses were constrained by limited validation cohort sizes, and mechanistic studies were limited to male mice, which may restrict the generalisability of our findings to female populations.

fundingNational Natural Science Foundation of China, Key Project of the Natural Science Foundation of Jiangsu Provincial Higher Education Institutions, Project of Biomedical Basic Research Center (BBRC) of Jiangsu, Clinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow University, Project of MOE Key Laboratory of Geriatric Diseases and Immunology, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases; The Lingang Laboratory fund; Shanghai Science and Technology Innovation Sailing Special Project, and Shanghai Municipal Science and Technology Major Project; Zhejiang Provincial Natural Science Foundation of China.

Indexed as

Complement C3DepressionMicrogliaParkinson DiseaseAnimalsBiomarkersDisease Models, AnimalFemaleHumansMaleMiceMice, KnockoutPhagocytosisProteomicsSignal TransductionBiomarkersComplement C3Botulinum neurotoxin AC3–C3aR signallingDepression in Parkinson's diseaseMicrogliaPlasma proteomicsSynaptic pruning

Identifiers

PMID42263400
PMCPMC13273220

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.