Evidence map›Paper›PMID 25108912›Full record

ArticleNature neuroscience2014

Polyglutamine-expanded androgen receptor interferes with TFEB to elicit autophagy defects in SBMA.

Constanza J Cortes, Helen C Miranda, Harald Frankowski, Yakup Batlevi, Jessica E Young, Amy Le, Nishi Ivanov, Bryce L Sopher, Cassiano Carromeu, Alysson R Muotri and 2 more

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

Article in Nature neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
7.7field-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

99 citing papers in PubMed, 170 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Polyglutamine expansion induced dynamic misfolding of androgen receptor.Protein science : a publication of the Protein Society · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Journal of bacteriology · 2024
    Article
  12. Article
  13. Review
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  15. Article
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  17. Article
  18. Article
  19. Review
  20. Bicalutamide and Trehalose Ameliorate Spinal and Bulbar Muscular Atrophy Pathology in Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Article

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Constanza J Cortes1] Department of Pediatrics, University of California, San Diego, La Jolla, California, USA. [2].
Helen C Miranda1] Department of Pediatrics, University of California, San Diego, La Jolla, California, USA. [2] Department of Cellular &Molecular Medicine, University of California, San Diego, La Jolla, California, USA. [3].
Harald FrankowskiDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Yakup BatleviDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Jessica E YoungDepartment of Cellular &Molecular Medicine, University of California, San Diego, La Jolla, California, USA.
Amy LeDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Nishi Ivanov1] Center on Human Development &Disability, University of Washington, Seattle, Washington, USA. [2] Department of Neurology, University of Washington, Seattle, Washington, USA.
Bryce L SopherDepartment of Neurology, University of Washington, Seattle, Washington, USA.
Cassiano CarromeuDepartment of Pediatrics, University of California, San Diego, La Jolla, California, USA.
Alysson R Muotri1] Department of Pediatrics, University of California, San Diego, La Jolla, California, USA. [2] Department of Cellular &Molecular Medicine, University of California, San Diego, La Jolla, California, USA. [3] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [4] Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA. [5] Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, California, USA. [6] Rady Children's Hospital, San Diego, California, USA.
Gwenn A Garden1] Center on Human Development &Disability, University of Washington, Seattle, Washington, USA. [2] Department of Neurology, University of Washington, Seattle, Washington, USA.
Albert R La Spada1] Department of Pediatrics, University of California, San Diego, La Jolla, California, USA. [2] Department of Cellular &Molecular Medicine, University of California, San Diego, La Jolla, California, USA. [3] Department of Neurosciences, University of California, San Diego, La Jolla, California, USA. [4] Institute for Genomic Medicine, University of California, San Diego, La Jolla, California, USA. [5] Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, California, USA. [6] Rady Children's Hospital, San Diego, California, USA. [7] Division of Biological Sciences, University of California, San Diego, La Jolla, California, USA.
University of California, San Diego · USUniversity of Washington · US

Funding

Vision Research CoreP30EY001730 · NEI · UNIVERSITY OF WASHINGTON · PI Jay Neitz · 1985 to 2026
$23.5M
MODELS OF SBMA MOTOR NEURON DEGENERATIONR01NS041648 · NINDS · UNIVERSITY OF WASHINGTON · PI LA SPADA, ALBERT R · 2001 to 2014
$4.5M
Project-002P30NS076411 · NINDS · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · PI LIPTON, STUART A · 2011 to 2016
$4.5M
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
Modeling autism with human pluripotent cellsDP2OD006495 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MUOTRI, ALYSSON R. · 2009 to 2009
$2.3M
NEI NIH HHS P30 EY001730NIA NIH HHS R01 AG033082NIH HHS DP2 OD006495NIH HHS DP2-OD006495-01NINDS NIH HHS P30 NS076411NINDS NIH HHS R01 NS041648
6 · The paper itself

Abstract

Macroautophagy (hereafter autophagy) is a key pathway in neurodegeneration. Despite protective actions, autophagy may contribute to neuron demise when dysregulated. Here we consider X-linked spinal and bulbar muscular atrophy (SBMA), a repeat disorder caused by polyglutamine-expanded androgen receptor (polyQ-AR). We found that polyQ-AR reduced long-term protein turnover and impaired autophagic flux in motor neuron-like cells. Ultrastructural analysis of SBMA mice revealed a block in autophagy pathway progression. We examined the transcriptional regulation of autophagy and observed a functionally significant physical interaction between transcription factor EB (TFEB) and AR. Normal AR promoted, but polyQ-AR interfered with, TFEB transactivation. To evaluate physiological relevance, we reprogrammed patient fibroblasts to induced pluripotent stem cells and then to neuronal precursor cells (NPCs). We compared multiple SBMA NPC lines and documented the metabolic and autophagic flux defects that could be rescued by TFEB. Our results indicate that polyQ-AR diminishes TFEB function to impair autophagy and promote SBMA pathogenesis.

Indexed as

AnimalsAutophagyBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCellular ReprogrammingDisease Models, AnimalFemaleFibroblastsHumansInduced Pluripotent Stem CellsMaleMice, TransgenicMotor NeuronsMuscular Disorders, AtrophicPeptidesPhagosomesReceptors, AndrogenAR protein, humanBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsPeptidespolyglutamineReceptors, AndrogenTcfeb protein, mouseTFEB protein, human

Identifiers

PMID25108912
PMCPMC4180729
OpenAlexW2090739159

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.