Evidence map›Paper›PMID 32242231›Full record

ArticleHuman molecular genetics2020

Nemo-like kinase reduces mutant huntingtin levels and mitigates Huntington's disease.

Mali Jiang, Xiaoyan Zhang, Hongshuai Liu, Jared LeBron, Athanasios Alexandris, Qi Peng, Hao Gu, Fanghan Yang, Yuchen Li, Ruiling Wang and 12 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 29% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies.International journal of molecular sciences · 2020
    Review
  10. 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

22 authors at 2 institutions in 1 country.

Mali JiangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Xiaoyan ZhangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hongshuai LiuDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jared LeBronDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Athanasios AlexandrisDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qi PengDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Hao GuDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Fanghan YangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yuchen LiDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ruiling WangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Zhipeng HouDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nicolas ArbezDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Qianwei RenDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jen-Li DongDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emma WhelaDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ronald WangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Tamara RatovitskiDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Juan C TroncosoDivision of Neuropathology, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Susumu MoriDepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Christopher A RossDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Janghoo LimDepartments of Genetics and of Neuroscience, Yale University School of Medicine, New Haven, CT, USA.
Wenzhen DuanDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Johns Hopkins University · USYale University · US

Funding

Validation of Novel Pathogenic Post-Translational Modifications of Huntingtin, and of Modifying Enzymes as Therapeutic Targets for Huntington's DiseaseR01NS086452 · NINDS · JOHNS HOPKINS UNIVERSITY · PI ROSS, CHRISTOPHER A · 2014 to 2023
$6.2M
Cellular and Molecular Studies of SBMA Neuromuscular DiseaseR01NS088321 · NINDS · YALE UNIVERSITY · PI LIM, JANGHOO · 2015 to 2019
$2.2M
Huntington's Disease biomarkers and therapeuticsR01NS082338 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN · 2013 to 2017
$2.0M
Investigating the Pathogenesis of Cerebellar NeurodegenerationR01NS083706 · NINDS · YALE UNIVERSITY · PI LIM, JANGHOO · 2014 to 2018
$1.8M
Structure of Triplet Repeat mRNA in Neurodegenerative DiseaseR01NS099397 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN, WOODSON, SARAH A. · 2016 to 2020
$1.8M
Imaging brain glucose uptake by onVDMP MRI in Huntington's DiseaseR21NS118079 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN, XU, JIADI · 2020 to 2020
$465k
Regulation of inhibitory interneuron developmentR21MH119803 · NIMH · YALE UNIVERSITY · PI LIM, JANGHOO · 2019 to 2020
$461k
Mitochondrial SIRT3 in Huntington's diseaseR21NS099670 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN · 2016 to 2017
$449k
Cerebrovascular Abnormalities in Huntington's DiseaseR21NS104480 · NINDS · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI DUAN, WENZHEN, HUA, JUN · 2018 to 2019
$446k
NG2 cells in Huntington's diseaseR21NS094886 · NINDS · JOHNS HOPKINS UNIVERSITY · PI DUAN, WENZHEN · 2016 to 2017
$446k
NIMH NIH HHS R21 MH119803NINDS NIH HHS R01 NS082338NINDS NIH HHS R01 NS083706NINDS NIH HHS R01 NS086452NINDS NIH HHS R01 NS088321NINDS NIH HHS R01 NS099397NINDS NIH HHS R21 NS094886NINDS NIH HHS R21 NS099670NINDS NIH HHS R21 NS104480NINDS NIH HHS R21 NS118079
6 · The paper itself

Abstract

Nemo-like kinase (NLK), an evolutionarily conserved serine/threonine kinase, is highly expressed in the brain, but its function in the adult brain remains not well understood. In this study, we identify NLK as an interactor of huntingtin protein (HTT). We report that NLK levels are significantly decreased in HD human brain and HD models. Importantly, overexpression of NLK in the striatum attenuates brain atrophy, preserves striatal DARPP32 levels and reduces mutant HTT (mHTT) aggregation in HD mice. In contrast, genetic reduction of NLK exacerbates brain atrophy and loss of DARPP32 in HD mice. Moreover, we demonstrate that NLK lowers mHTT levels in a kinase activity-dependent manner, while having no significant effect on normal HTT protein levels in mouse striatal cells, human cells and HD mouse models. The NLK-mediated lowering of mHTT is associated with enhanced phosphorylation of mHTT. Phosphorylation defective mutation of serine at amino acid 120 (S120) abolishes the mHTT-lowering effect of NLK, suggesting that S120 phosphorylation is an important step in the NLK-mediated lowering of mHTT. A further mechanistic study suggests that NLK promotes mHTT ubiquitination and degradation via the proteasome pathway. Taken together, our results indicate a protective role of NLK in HD and reveal a new molecular target to reduce mHTT levels.

Indexed as

AnimalsAtrophyBrainCorpus StriatumDisease Models, AnimalDopamine and cAMP-Regulated Phosphoprotein 32HumansHuntingtin ProteinHuntington DiseaseMiceNeostriatumNeuronsPhosphorylationProteasome Endopeptidase ComplexProtein Serine-Threonine KinasesDopamine and cAMP-Regulated Phosphoprotein 32Htt protein, mouseHuntingtin ProteinNlk protein, mousePpp1r1b protein, mouseProteasome Endopeptidase ComplexProtein Serine-Threonine Kinases

Identifiers

PMID32242231
PMCPMC7254850
OpenAlexW3014284868

What OpenQuestion holds

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Registered trials

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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.