Evidence map›Paper›PMID 41813972›Full record

ArticleActa pharmacologica Sinica2026

Sonic Hedgehog-Gli1 signaling promotes microglial activation via the IKKβ/NF-κB pathway.

Zhi-Rou Xu, Kan Wu, Rui-Ying Guo, Peng Wang, Jia-Wei Ou-Yang, Zhong-Qiang Cao, Hui-Cui Yang, Jong-Heon Kim, Xiao-Hu Zhang, Kyoungho Suk and 4 more

Abstract read
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In one paragraph

Article in Acta pharmacologica Sinica, 2026. 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

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

1 citing paper in PubMed.

  1. Article
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

14 authors.

Zhi-Rou XuThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Kan WuThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Rui-Ying GuoThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Peng WangThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Jia-Wei Ou-YangThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Zhong-Qiang CaoThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Hui-Cui YangThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Jong-Heon KimDepartment of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
Xiao-Hu ZhangThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Kyoungho SukDepartment of Pharmacology, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
Xue-Chu ZhenThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Yuan WangThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. yuanw@suda.edu.cn.
Xiang-Dong DuThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. xiangdong-du@163.com.
Long-Tai ZhengThe Affiliated Guangji Hospital of Soochow University, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China. zhenglongtai@suda.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Sonic Hedgehog (Shh)-Gli1 signaling axis is essential for neuronal development, cell proliferation and homeostasis. However, its roles in microglial activation and neuroinflammation remain poorly defined. Here, we report that Shh is expressed in neurons and astrocytes and is markedly upregulated in the substantia nigra of MPTP-challenged Parkinson's disease (PD) mouse models. In contrast, microglia do not produce Shh but express its receptor Patched1 (PTCH1) and downstream effectors, including Smoothened (SMO) and Gli1. Exogenous treatment with recombinant Shh or the SMO agonist SAG induced low-level microglial activation and amplified LPS-driven inflammatory responses via the Shh-Gli1-IKKβ signaling pathway. Moreover, we found that Shh-Gli1 signaling contributes to LPS-induced microglial activation. Genetic or pharmacological inhibition of this pathway suppressed microglial activation by attenuating NF-κB signaling. Notably, treatment with the small-molecule SMO inhibitor GDC-0449 (vismodegib) alleviated neuroinflammation and protected dopaminergic neurons in mice subjected to intracranial LPS challenge. Conversely, microglia-specific Ptch1 knockout exacerbated susceptibility to LPS-induced neuroinflammation and dopaminergic neuronal loss. Collectively, these findings demonstrate that microglial Shh-Gli1 signaling promotes microglial inflammatory activation, establishing the pivotal role of this pathway in microglia-driven neuroinflammation and subsequent dopaminergic neuronal injuries.

Indexed as

Hedgehog ProteinsI-kappa B KinaseMicrogliaNF-kappa BSignal TransductionZinc Finger Protein GLI1AnilidesAnimalsLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutPatched-1 ReceptorPyridinesSmoothened ReceptorAnilidesGli1 protein, mouseHedgehog ProteinsHhAntag691I-kappa B KinaseIkbkb protein, mouseLipopolysaccharidesNF-kappa BPatched-1 ReceptorPtch1 protein, mousePyridinesShh protein, mouseSmoothened ReceptorSmo protein, mouseZinc Finger Protein GLI1microglianeuroinflammationNF-κB pathwayParkinson's diseaseSonic Hedgehog signaling

Identifiers

PMID41813972
PMCPMC13279993

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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.