Evidence map›Paper›PMID 36670138›Full record

ArticleScientific reports2023

Neuronal glutathione loss leads to neurodegeneration involving gasdermin activation.

Shoko Hashimoto, Yukio Matsuba, Mika Takahashi, Naoko Kamano, Naoto Watamura, Hiroki Sasaguri, Yuhei Takado, Yoshihiro Yoshihara, Takashi Saito, Takaomi C Saido

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Redox Molecules in Aging and Neurodegenerative Disorders.International journal of molecular sciences · 2026
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
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

10 authors at 3 institutions in 1 country.

Shoko HashimotoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. shokoh@belle.shiga-med.ac.jp.
Yukio MatsubaLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Mika TakahashiLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Naoko KamanoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Naoto WatamuraLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Hiroki SasaguriLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Yuhei TakadoDepartment of Functional Brain Imaging, National Institutes for Quantum Science and Technology, 4-9-1 Anagawa, Inage-Ku, Chiba, 263-8555, Japan.
Yoshihiro YoshiharaLaboratory for Systems Molecular Ethology, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Takashi SaitoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Takaomi C SaidoLaboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan. takaomi.saido@riken.jp.
RIKEN Center for Brain Science · JPNational Institutes for Quantum Science and Technology · JPShiga University of Medical Science · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulating evidence suggests that glutathione loss is closely associated with the progression of neurodegenerative disorders. Here, we found that the neuronal conditional-knockout (KO) of glutamyl-cysteine-ligase catalytic-subunit (GCLC), a rate-limiting enzyme for glutathione synthesis, induced brain atrophy accompanied by neuronal loss and neuroinflammation. GCLC-KO mice showed activation of C1q, which triggers engulfment of neurons by microglia, and disease-associated-microglia (DAM), suggesting that activation of microglia is linked to the neuronal loss. Furthermore, gasdermins, which regulate inflammatory form of cell death, were upregulated in the brains of GCLC-KO mice, suggesting the contribution of pyroptosis to neuronal cell death in these animals. In particular, GSDME-deficiency significantly attenuated the hippocampal atrophy and changed levels of DAM markers in GCLC-KO mice. Finally, we found that the expression of GCLC was decreased around amyloid plaques in App

Indexed as

GasderminsNeuroinflammatory DiseasesAnimalsBrainGlutathioneMiceOxidative StressGasderminsGlutathione

Identifiers

PMID36670138
PMCPMC9859798
OpenAlexW4317569231

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.