Evidence map›Paper›PMID 25952542›Full record

ArticleMolecular neurobiology2016

Formation and Implications of Alpha-Synuclein Radical in Maneb- and Paraquat-Induced Models of Parkinson's Disease.

Ashutosh Kumar, Fabian Leinisch, Maria B Kadiiska, Jean Corbett, Ronald P Mason

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

Article in Molecular neurobiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.7field-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

30 citing papers in PubMed, 59 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Parkinson's Disease: Exploring Different Animal Model Systems.International journal of molecular sciences · 2023
    Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
  12. TheBioMed research international · 2020
    Article
  13. Article
  14. Review
  15. Article
  16. Effects of paraquat on IL-6 and TNF-α in macrophages.Experimental and therapeutic medicine · 2019
    Article
  17. Article
  18. Article
  19. Article
  20. Article
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

5 authors at 1 institution in 1 country.

Ashutosh KumarFree Radical Metabolism Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA. kumara10@niehs.nih.gov.
Fabian LeinischFree Radical Metabolism Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
Maria B KadiiskaFree Radical Metabolism Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
Jean CorbettFree Radical Metabolism Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
Ronald P MasonFree Radical Metabolism Group, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
National Institute of Environmental Health Sciences · US

Funding

Protein Derived RadicalsZIAES050139 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MASON, RONALD P · 2009 to 2018
$17.5M
In Vivo Detection of Free Radical GenerationZIAES050117 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MASON, RONALD P · 2009 to 2018
$6.9M
TRANSITION-METAL MEDIATED FREE RADICAL FORMATION IN VITRO AND IN VIVOZ01ES050117 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI MASON, RONALD P · 1991 to 2008
$2.2M
Intramural NIH HHS Z01 ES050117Intramural NIH HHS ZIA ES050139
6 · The paper itself

Abstract

Parkinson's disease (PD) is a debilitating, progressive, neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and motor deficits. Alpha-synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including PD; however, the mechanism that initiates and promotes intraneuronal alpha-synuclein aggregation remains unknown. We hypothesized protein radical formation as an initiating mechanism for alpha-synuclein aggregation. Therefore, we used the highly sensitive immuno-spin trapping technique to investigate protein radical formation as a possible mechanism of alpha-synuclein aggregation as well as to investigate the source of protein radical formation in the midbrains of Maneb- and paraquat-coexposed mice. Coexposure to Maneb and paraquat for 6 weeks resulted in active microgliosis, NADPH oxidase activation, and inducible nitric oxide synthase (iNOS) induction, which culminated in protein radical formation in the midbrains of mice. Results obtained with immuno-spin trapping and immunoprecipitation experiments confirmed formation of alpha-synuclein radicals in dopaminergic neurons of exposed mice. Free radical formation requires NADPH oxidase and iNOS, as indicated by decreased protein radical formation in knockout mice (P47phox(-/-) and iNOS(-/-)) and in mice treated with inhibitors such as FeTPPS (a peroxynitrite decomposition catalyst), 1400 W (an iNOS inhibitor), or apocynin (a NADPH oxidase inhibitor). Concurrence of protein radical formation with dopaminergic neuronal death indicated a link between protein radicals and disease progression. Taken together, these results show for the first time the formation and detection of the alpha-synuclein radical and suggest that NADPH oxidase and iNOS play roles in peroxynitrite-mediated protein radical formation and subsequent neuronal death in the midbrains of Maneb- and paraquat-coexposed mice.

Indexed as

alpha-SynucleinAnimalsCyclic N-OxidesDisease Models, AnimalDopaminergic NeuronsInjections, IntraperitonealMaleManebMesencephalonMice, Inbred C57BLMicrogliaModels, BiologicalNADPH OxidasesNitric Oxide Synthase Type IIParaquatParkinson Disease5,5-dimethyl-1-pyrroline-1-oxidealpha-SynucleinCyclic N-OxidesManebNADPH OxidasesNitric Oxide Synthase Type IIParaquatPeroxynitrous AcidSpin LabelsTyrosine 3-MonooxygenaseDMPOImmuno-spin trappingParkinson’s diseasePeroxynitriteProtein radicals

Identifiers

PMID25952542
PMCPMC4637265
OpenAlexW803885568

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.