Evidence map›Paper›PMID 26642438›Full record

ArticleNature medicine2016

PPAR-δ is repressed in Huntington's disease, is required for normal neuronal function and can be targeted therapeutically.

Audrey S Dickey, Victor V Pineda, Taiji Tsunemi, Patrick P Liu, Helen C Miranda, Stephen K Gilmore-Hall, Nicole Lomas, Kunal R Sampat, Anne Buttgereit, Mark-Joseph Manalang Torres and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

56 citing papers in PubMed, 106 citations in OpenAlex.

  1. Review
  2. Article
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  6. Article
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  8. Article
  9. Review
  10. Article
  11. Review
  12. Bilirubin and Redox Stress in Age-Related Brain Diseases.Antioxidants (Basel, Switzerland) · 2023
    Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. HSF1 and Its Role in Huntington's Disease Pathology.Advances in experimental medicine and biology · 2023
    Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 1 country.

Audrey S DickeyDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Victor V PinedaDepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Taiji TsunemiDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Patrick P LiuDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA.
Helen C MirandaDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Stephen K Gilmore-HallDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Nicole LomasDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Kunal R SampatDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Anne ButtgereitDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Mark-Joseph Manalang TorresDepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
April L FloresDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
Martin ArreolaDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.ORCID http://orcid.org/0000-0002-7630-1403
Nicolas ArbezDivision of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID http://orcid.org/0000-0003-1038-192X
Sergey S AkimovDivision of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Terry GaasterlandSanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California, USA.
Eduardo R LazarowskiDepartment of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Christopher A RossDivision of Neurobiology, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Gene W YeoDepartment of Cellular and Molecular Medicine, University of California San Diego, La Jolla, California, USA.
Bryce L SopherDepartment of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
Gavin K MagnusonSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.
Anthony B PinkertonSanford-Burnham-Prebys Medical Discovery Institute, La Jolla, California, USA.
Eliezer MasliahDepartment of Pathology, University of California San Diego, La Jolla, California, USA.
Albert R La SpadaDepartment of Pediatrics, University of California San Diego, La Jolla, California, USA.
University of California San Diego · USJohns Hopkins University · USUniversity of Washington · USSanford Burnham Prebys Medical Discovery Institute · USScripps Institution of Oceanography · USUniversity of North Carolina at Chapel Hill · US

Funding

Functional RNA elements in the human genomeR01HG004659 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Kevin Daniel Corbett, Eugene Wei-Ming Yeo · 2008 to 2026
$12.4M
Purinergic Control of CFTR-ENaC Interactions in Alveolar EpitheliaP01HL110873 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES · 2012 to 2016
$10.7M
The PPAR-delta pathway in neural function and Huntington's disease neuropathologyR01NS065874 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LA SPADA, ALBERT R · 2010 to 2020
$4.0M
Molecular genetic regulation of autophagy in health and neurodegenerative diseaseR01AG033082 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LA SPADA, ALBERT R · 2009 to 2019
$4.0M
Genomes in Eye Disease: Methods to Query Variants Across Multiple Genome-wide DatR01EY022306 · NEI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GAASTERLAND, THERESA · 2012 to 2014
$1.0M
Modulation of the PPAR-delta Signaling Pathway in Huntingtons DiseaseF32NS081964 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DICKEY, AUDREY S · 2012 to 2014
$157k
NEI NIH HHS R01 EY022306NHGRI NIH HHS R01 HG004659NHLBI NIH HHS P01 HL110873NIA NIH HHS R01 AG033082NINDS NIH HHS F32 NS081964NINDS NIH HHS R01 NS065874
6 · The paper itself

Abstract

Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene, which encodes a polyglutamine tract in the HTT protein. We found that peroxisome proliferator-activated receptor delta (PPAR-δ) interacts with HTT and that mutant HTT represses PPAR-δ-mediated transactivation. Increased PPAR-δ transactivation ameliorated mitochondrial dysfunction and improved cell survival of neurons from mouse models of HD. Expression of dominant-negative PPAR-δ in the central nervous system of mice was sufficient to induce motor dysfunction, neurodegeneration, mitochondrial abnormalities and transcriptional alterations that recapitulated HD-like phenotypes. Expression of dominant-negative PPAR-δ specifically in the striatum of medium spiny neurons in mice yielded HD-like motor phenotypes, accompanied by striatal neuron loss. In mouse models of HD, pharmacologic activation of PPAR-δ using the agonist KD3010 improved motor function, reduced neurodegeneration and increased survival. PPAR-δ activation also reduced HTT-induced neurotoxicity in vitro and in medium spiny-like neurons generated from stem cells derived from individuals with HD, indicating that PPAR-δ activation may be beneficial in HD and related disorders.

Indexed as

AnimalsCell DeathChromatin ImmunoprecipitationDisease Models, AnimalGene Expression ProfilingHEK293 CellsHumansHuntingtin ProteinHuntington DiseaseInduced Pluripotent Stem CellsIn Vitro TechniquesMiceMice, TransgenicMitochondriaMovementNeostriatum4-(2,6-dimethyl-4-(4-trifluoromethoxyphenyl)piperazine-1-sulfonyl)indan-2-carboxylic acidHTT protein, humanHuntingtin ProteinNerve Tissue ProteinsPiperazinesPPAR deltaPpard protein, mouseReceptors, Cytoplasmic and NuclearSulfonamides

Identifiers

PMID26642438
PMCPMC4752002
OpenAlexW2191305454

What OpenQuestion holds

Textmetadata
LicenceTDM
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.