Evidence map›Paper›PMID 25533483›Full record

ArticleNeuron2015

Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on α-synuclein.

Nripesh Dhungel, Simona Eleuteri, Ling-Bo Li, Nicholas J Kramer, Justin W Chartron, Brian Spencer, Kori Kosberg, Jerel Adam Fields, Klodjan Stafa, Anthony Adame and 5 more

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

Article in Neuron, 2015. 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 99 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 2 pooled it
15.6field-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, 2 syntheses or guidelines pooled it, 178 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Cellular and systemic modifiers of alpha-synuclein proteostasis.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. VPS35 and retromer dysfunction in Parkinson's disease.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Genetics and Pathogenesis of Parkinson's Syndrome.Annual review of pathology · 2023
    Review
  16. Review
  17. Receptor Recycling by Retromer.Molecular and cellular biology · 2023
    Review
  18. Review
  19. Article
  20. 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

15 authors at 4 institutions in 2 countries.

Nripesh DhungelDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Simona EleuteriDepartment of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Ling-Bo LiDepartment of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA.
Nicholas J KramerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Justin W ChartronDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
Brian SpencerDepartment of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Kori KosbergDepartment of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Jerel Adam FieldsDepartment of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Klodjan StafaDepartment of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Anthony AdameDepartment of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.
Hilal LashuelLaboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, Station 19, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, (EPFL) CH-1015 Lausanne, Switzerland.
Judith FrydmanDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
Kang ShenDepartment of Biology, Stanford University, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford, CA 94305, USA.
Eliezer MasliahDepartment of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA; Department of Pathology, School of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. Electronic address: emasliah@ucsd.edu.
Aaron D GitlerDepartment of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: agitler@stanford.edu.
University of California, San Diego · USStanford University · USHoward Hughes Medical Institute · USÉcole Polytechnique Fédérale de Lausanne · CH

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GALASKO, DOUGLAS R · 1985 to 2018
$55.4M
Tissue Culture CoreP01AG022074 · NIA · J. DAVID GLADSTONE INSTITUTES · PI MASLIAH, ELIEZER · 2003 to 2012
$27.0M
Viral VectorsP01AG010435 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUSZYNSKI, MARK H. · 1991 to 2014
$20.9M
Training Program in Basic NeuroscienceT32MH020016 · NIMH · STANFORD UNIVERSITY · PI Justin L Gardner, Merritt C Maduke · 1997 to 2026
$16.2M
Mechanisms of Neuroprotection in HIV EncephalitisR01MH062962 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2002 to 2016
$5.2M
B-Synuclein as a Treatment for Lewy Body DiseaseR01AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI RISSMAN, ROBERT · 2001 to 2021
$5.2M
Protein Folding in the Eukaryotic CytosolR37GM056433 · NIGMS · STANFORD UNIVERSITY · PI FRYDMAN, JUDITH · 2013 to 2022
$4.6M
Project-002P30NS076411 · NINDS · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · PI LIPTON, STUART A · 2011 to 2016
$4.5M
A Stanford - SJSU Postdoctoral Training Program to Enhance URM TeachingK12GM088033 · NIGMS · STANFORD UNIVERSITY · PI BOOTHROYD, JOHN C · 2010 to 2016
$4.1M
a-synuclein clearance strategies for the treatment of Lewy body disease.R37AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2006 to 2014
$2.7M
Molecular Basis of TDP-43 Proteinopathies: Disease Models and MechanismsR01NS065317 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI GITLER, AARON D. · 2009 to 2016
$2.7M
Clearance Pathways in the CNS in Aging and HIVR01AG043384 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DESPLATS, PAULA ALEJANDRA · 2012 to 2016
$1.9M
NIA NIH HHS 1R01AG18440NIA NIH HHS P01 AG010435NIA NIH HHS P01 AG022074NIA NIH HHS P50 AG005131NIA NIH HHS R01 AG018440NIA NIH HHS R01 AG043384NIA NIH HHS R37 AG018440NIGMS NIH HHS K12 GM088033NIGMS NIH HHS K12-GM088033NIGMS NIH HHS R37 GM056433NIMH NIH HHS R01 MH062962NIMH NIH HHS T32 MH020016NINDS NIH HHS 1R01NS065317NINDS NIH HHS 1R01NS07366NINDS NIH HHS P30 NS076411NINDS NIH HHS R01 NS065317NINDS NIH HHS T32 NS007366
6 · The paper itself

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder. Functional interactions between some PD genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1, and α-synuclein, a protein with a key role in PD. We extend our findings from yeast to an animal model and show that these interactions are conserved in neurons and in transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to α-synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future interrogation. VIDEO ABSTRACT:

Indexed as

Adaptor Proteins, Vesicular Transportalpha-SynucleinAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsEukaryotic Initiation Factor-4GMiceMice, TransgenicParkinson DiseaseSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSortilinVesicular Transport ProteinsAdaptor Proteins, Vesicular Transportalpha-SynucleinCaenorhabditis elegans ProteinsEif4g1 protein, mouseEukaryotic Initiation Factor-4GSaccharomyces cerevisiae ProteinsSortilinVesicular Transport ProteinsVps35 protein, mouse

Identifiers

PMID25533483
PMCPMC4289081
OpenAlexW2014397333

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.