Evidence map›Paper›PMID 29786071›Full record

ArticleCell death and differentiation2018

Dopamine D2 receptor restricts astrocytic NLRP3 inflammasome activation via enhancing the interaction of β-arrestin2 and NLRP3.

Jialei Zhu, Zhaoli Hu, Xiaojuan Han, Dongshuo Wang, Qingling Jiang, Jianhua Ding, Ming Xiao, Cong Wang, Ming Lu, Gang Hu

Open access · bronzeAbstract read
In one paragraph

Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 2 pooled it
9.5field-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

92 citing papers in PubMed, 2 syntheses or guidelines pooled it, 164 citations in OpenAlex.

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32 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

10 authors at 2 institutions in 1 country.

Jialei ZhuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Zhaoli HuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Xiaojuan HanDepartment of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu, 210023, China.
Dongshuo WangDepartment of Pharmacology, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu, 210023, China.
Qingling JiangJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Jianhua DingJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Ming XiaoJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Cong WangJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China.
Ming LuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China. lum@njmu.edu.cn.
Gang HuJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 101 Longmian Avenue, Nanjing, Jiangsu, 211166, China. ghu@njmu.edu.cn.
Nanjing Medical University · CNNanjing University of Chinese Medicine · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1β (IL-1β) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. β-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system. However, the role of Drd2 in astrocytic NLRP3 inflammasome activation and subsequent IL-1β production remains unclear. In the present study, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced PD mouse model to investigate whether Drd2 could suppress astrocytic NLRP3 inflammasome activation. We showed that Drd2 agonist inhibited NLRP3 inflammasome activation, evidenced by decreased caspase-1 expression and reduced IL-1β release in the midbrain of wild type mice. The anti-inflammasome effect of Drd2 was abolished in β-arrestin2 knockout and β-arrestin2 small interfering RNA-injected mice, suggesting a critical role of β-arrestin2 in Drd2-regulated NLRP3 inflammasome activation. We also found that Drd2 agonists suppressed the upregulation of caspase-1 and IL-1β expression in primary cultured mouse astrocytes in response to the activation of NLRP3 inflammasome induced by lipopolysaccharide plus adenosine triphosphate. Furthermore, we demonstrated that β-arrestin2 mediated the inhibitory effect of Drd2 on NLRP3 inflammasome activation via interacting with NLRP3 and interfering the inflammasome assembly. Collectively, our study illustrates that astrocytic Drd2 inhibits NLRP3 inflammasome activation through a β-arrestin2-dependent mechanism, and provides a new strategy for treatment of PD.

Indexed as

Adenosine TriphosphateAnimalsAstrocytesbeta-Arrestin 2Caspase 1Cells, CulturedDisease Models, AnimalInflammasomesInterleukin-1betaLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinParkinson Disease, SecondaryAdenosine Triphosphatebeta-Arrestin 2Caspase 1InflammasomesInterleukin-1betaLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinReceptors, Dopamine D2RNA, Small Interfering

Identifiers

PMID29786071
PMCPMC6219479
OpenAlexW2804137773

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.