Evidence map›Paper›PMID 26894491›Full record

ArticleBiochemistry2016

Regulation of DJ-1 by Glutaredoxin 1 in Vivo: Implications for Parkinson's Disease.

William M Johnson, Marcin Golczak, Kyonghwan Choe, Pierce L Curran, Olga Gorelenkova Miller, Chen Yao, Wenzhang Wang, Jiusheng Lin, Nicole M Milkovic, Ajit Ray and 6 more

Abstract read
In one paragraph

Article in Biochemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 8% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.

  1. Pooled it
  2. HSPBiomedicines · 2025
    Article
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  5. Article
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  9. Redox RegulationAntioxidants & redox signaling · 2020
    Review
  10. Article
  11. Article
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  13. Review
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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

16 authors at 4 institutions in 2 countries.

William M Johnson
Marcin Golczak
Kyonghwan Choe
Pierce L Curran
Olga Gorelenkova Miller
Chen Yao
Wenzhang Wang
Jiusheng LinDepartment of Biochemistry and the Redox Biology Center, University of Nebraska-Lincoln , Lincoln, Nebraska 68588, United States.
Nicole M MilkovicDepartment of Biochemistry and the Redox Biology Center, University of Nebraska-Lincoln , Lincoln, Nebraska 68588, United States.
Ajit RayCentre for Neuroscience, Indian Institute of Science , C.V. Raman Avenue, Bangalore 560012, India.
Vijayalakshmi RavindranathCentre for Neuroscience, Indian Institute of Science , C.V. Raman Avenue, Bangalore 560012, India.
Xiongwei Zhu
Mark A WilsonDepartment of Biochemistry and the Redox Biology Center, University of Nebraska-Lincoln , Lincoln, Nebraska 68588, United States.
Amy L Wilson-Delfosse
Shu G Chen
John J MieyalLouis B. Stokes Veterans Affairs Medical Research Center , Cleveland, Ohio 44106, United States.
Case Western Reserve University · USUniversity of Nebraska–Lincoln · USIndian Institute of Science Bangalore · INLouis Stokes Cleveland VA Medical Center · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
PREDOCTORAL TRAINING PROGRAM IN MOLECULAR THERAPEUTICST32GM008803 · NIGMS · CASE WESTERN RESERVE UNIVERSITY · PI MIEYAL, JOHN J, NIEMAN, MARVIN THOMAS · 2001 to 2023
$4.2M
Regulation of vitamin A metabolism in the eyeR01EY023948 · NEI · CASE WESTERN RESERVE UNIVERSITY · PI GOLCZAK, MARCIN BERNARD · 2014 to 2023
$3.8M
Redox Regulation of DJ-1 FunctionR01GM092999 · NIGMS · UNIVERSITY OF NEBRASKA LINCOLN · PI WILSON, MARK A. · 2010 to 2014
$1.3M
Epigenomic Mechanism of Parkinson's DiseaseR01NS083498 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI ZHU, XIONGWEI · 2013 to 2015
$604k
Glutaredoxin, a Critical Regulator of Parkinson Disease PathogenesisR21NS085503 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI CHEN, SHU G., MIEYAL, JOHN J · 2013 to 2014
$434k
Assay Development and Discovery of LRRK2 Inhibitors for Parkinson DiseaseR21NS073170 · NINDS · CASE WESTERN RESERVE UNIVERSITY · PI CHEN, SHU G. · 2010 to 2011
$428k
Enzymatic Regulation of S-Glutathionylation : Role in Apoptosis and DiseaseI01BX000290 · VA · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · PI MIEYAL, JOHN J · 2011 to 2012
–
BLRD VA I01 BX000290NCATS NIH HHS UL1 TR000439NEI NIH HHS R01 EY023948NIGMS NIH HHS R01 GM092999NIGMS NIH HHS T32 GM008803NIH HHS P40 OD010440NINDS NIH HHS R01 NS083498NINDS NIH HHS R21 NS073170NINDS NIH HHS R21 NS085503Parkinson''s Disease Foundation PDF-SFW-1348Parkinson''s Disease Foundation PDF-SFW-1566
6 · The paper itself

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, caused by the degeneration of the dopaminergic neurons in the substantia nigra. Mutations in PARK7 (DJ-1) result in early onset autosomal recessive PD, and oxidative modification of DJ-1 has been reported to regulate the protective activity of DJ-1 in vitro. Glutathionylation is a prevalent redox modification of proteins resulting from the disulfide adduction of the glutathione moiety to a reactive cysteine-SH, and glutathionylation of specific proteins has been implicated in regulation of cell viability. Glutaredoxin 1 (Grx1) is the principal deglutathionylating enzyme within cells, and it has been reported to mediate protection of dopaminergic neurons in Caenorhabditis elegans; however many of the functional downstream targets of Grx1 in vivo remain unknown. Previously, DJ-1 protein content was shown to decrease concomitantly with diminution of Grx1 protein content in cell culture of model neurons (SH-SY5Y and Neuro-2A lines). In the current study we aimed to investigate the regulation of DJ-1 by Grx1 in vivo and characterize its glutathionylation in vitro. Here, with Grx(-/-) mice we provide show that Grx1 regulates protein levels of DJ-1 in vivo. Furthermore, with model neuronal cells (SH-SY5Y) we observed decreased DJ-1 protein content in response to treatment with known glutathionylating agents, and with isolated DJ-1 we identified two distinct sites of glutathionylation. Finally, we found that overexpression of DJ-1 in the dopaminergic neurons partly compensates for the loss of the Grx1 homologue in a C. elegans in vivo model of PD. Therefore, our results reveal a novel redox modification of DJ-1 and suggest a novel regulatory mechanism for DJ-1 content in vivo.

Indexed as

Amino Acid SequenceAnimalsCaenorhabditis elegansCell Line, TumorCysteineGlutaredoxinsGlutathioneHumansMiceParkinson DiseaseProtein Deglycase DJ-1Protein Processing, Post-TranslationalCysteineGlutaredoxinsGlutathioneProtein Deglycase DJ-1

Identifiers

PMID26894491
PMCPMC4987251
OpenAlexW2277886163

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.