Evidence mapPaperPMID 41881908Full record

ArticleCell death & disease2026

Complement receptor 3 (CR3)-dependent microglial synapse elimination drives Parkinson's disease pathogenesis in systemic inflammation.

Lei Cai, Yihe Zhang, Jiayi Li, Lamei Hu, Qinghao Meng, Jingyi Shao, Haotian Deng, Yiying Liu, Jiaqi Liu, Yue Liang and 6 more

Abstract read
In one paragraph

Article in Cell death & disease, 2026. 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. Article
  2. 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

16 authors.

Lei Cai *Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Yihe Zhang *Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Jiayi LiJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Lamei HuDepartment of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Qinghao MengJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Jingyi ShaoJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Haotian DengJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Yiying LiuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Jiaqi LiuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Yue LiangJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Nanshan SongDepartment of Pharmacology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
Jianhua DingJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.
Yi FanJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0003-1783-3220
Ming LuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China.ORCID http://orcid.org/0000-0001-8018-8389
Yinquan FangJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China. fangyinquan26@njmu.edu.cn.ORCID http://orcid.org/0000-0003-4814-7960
Gang HuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, Jiangsu, China. ghu@njmu.edu.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81703488National Natural Science Foundation of China (National Science Foundation of China) 81991523
6 · The paper itself

Abstract

Although systemic inflammation has been implicated in PD pathogenesis, the underlying mechanisms remain poorly understood. In this study, we investigate the pathological events in a systemic inflammation-induced PD mouse model. We demonstrate that synaptic loss in the midbrain occurs as early as 1 day after the final lipopolysaccharide (LPS) administration, preceding dopaminergic (DA) neuron degeneration, which was observed only at later stages (14 days). Early microglial activation in the midbrain is detected, accompanied by excessive synaptic engulfment, suggesting a critical role of microglia-dependent synapse elimination in PD pathogenesis. Furthermore, we identify the complement receptor 3 (CR3) as a key mediator of microglial synaptic engulfment, revealing that its inhibition rescues synaptic integrity and prevents neurodegeneration. Our results contribute to a deeper understanding of early events of PD progression driven by systemic inflammation and provide early intervention strategies targeting microglial complement signaling to halt PD progression.

Indexed as

InflammationMacrophage-1 AntigenMicrogliaParkinson DiseaseSynapsesAnimalsDisease Models, AnimalDopaminergic NeuronsLipopolysaccharidesMaleMiceMice, Inbred C57BLLipopolysaccharidesMacrophage-1 Antigen

Identifiers

PMID41881908
PMCPMC13039679

What Socratic 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 Socratic graph.