Evidence map›Paper›PMID 29608652›Full record

ArticleBrain : a journal of neurology2018

Targeting Gpr52 lowers mutant HTT levels and rescues Huntington's disease-associated phenotypes.

Haikun Song, Hexuan Li, Shimeng Guo, Yuyin Pan, Yuhua Fu, Zijian Zhou, Zhaoyang Li, Xue Wen, Xiaoli Sun, Bingqing He and 8 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain : a journal of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Research Progress of G Protein-coupled Receptor 52 on Central Nervous System Diseases.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2026
    Review
  3. The genetic architecture of fibromyalgia across 2.5 million individuals.medRxiv : the preprint server for health sciences · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 4 institutions in 2 countries.

Haikun SongNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Hexuan LiNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Shimeng GuoCAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yuyin PanNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Yuhua FuNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Zijian ZhouNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Zhaoyang LiNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Xue WenNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Xiaoli SunNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Bingqing HeCAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Haifeng GuCAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Quan ZhaoNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Cen WangNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Ping AnNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Shouqing LuoPeninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, University of Plymouth, Research Way, Plymouth, UK.
Youhong HuCAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Xin XieCAS Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Boxun LuNeurology Department at Huashan Hospital, State Key Laboratory of Medical Neurobiology, School of Life Sciences, Fudan University, Shanghai, China.
Fudan University · CNShanghai Institute of Materia Medica · CNShanghaiTech University · CNUniversity of Plymouth · GB

Funding

Medical Research Council MR/M023605/1
6 · The paper itself

Abstract

See Huang and Gitler (doi:10.1093/brain/awy112) for a scientific commentary on this article.Lowering the levels of disease-causing proteins is an attractive treatment strategy for neurodegenerative disorders, among which Huntington's disease is an appealing disease for testing this strategy because of its monogenetic nature. Huntington's disease is mainly caused by cytotoxicity of the mutant HTT protein with an expanded polyglutamine repeat tract. Lowering the soluble mutant HTT may reduce its downstream toxicity and provide potential treatment for Huntington's disease. This is hard to achieve by small-molecule compound drugs because of a lack of effective targets. Here we demonstrate Gpr52, an orphan G protein-coupled receptor, as a potential Huntington's disease drug target. Knocking-out Gpr52 significantly reduces mutant HTT levels in the striatum and rescues Huntington's disease-associated behavioural phenotypes in a knock-in Huntington's disease mouse model expressing endogenous mutant Htt. Importantly, a novel Gpr52 antagonist E7 reduces mutant HTT levels and rescues Huntington's disease-associated phenotypes in cellular and mouse models. Our study provides an entry point for Huntington's disease drug discovery by targeting Gpr52.

Indexed as

Age FactorsAnimalsBenzamidesCorpus StriatumCyclic AMPDisease Models, AnimalDrosophilaDrosophila ProteinsExploratory BehaviorGaitHEK293 CellsHumansHuntingtin ProteinHuntington DiseaseInduced Pluripotent Stem CellsMice3-(2-(3-chloro-5-fluorobenzyl)-1-benzothiophen-7-yl)-N-(2-methoxyethyl)benzamideBenzamidesCyclic AMPDrosophila ProteinsGPR52 protein, humanHuntingtin ProteinN-(2-hydroxyethyl)-3-methyl-2-quinoxalincarboxamideQuinoxalinesReceptors, G-Protein-CoupledThiophenes

Identifiers

PMID29608652
PMCPMC5972579
OpenAlexW2794666635

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.