Evidence map›Paper›PMID 29895691›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2018

Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis.

Brienne A McKenzie, Manmeet K Mamik, Leina B Saito, Roobina Boghozian, Maria Chiara Monaco, Eugene O Major, Jian-Qiang Lu, William G Branton, Christopher Power

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. 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 294 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
294citing papers in PubMed, 1 pooled it
16.7field-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

294 citing papers in PubMed, 1 synthesis or guideline pooled it, 527 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Review
  11. Cell death in multiple sclerosis.Cell death and differentiation · 2026
    Review
  12. Article
  13. Immune Aging as a Failure of Programmed Cell Death Coordination.International journal of molecular sciences · 2026
    Review
  14. De novo discovery of bicyclic cysteine-rich peptides targeting gasdermin D.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Brienne A McKenzieDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Manmeet K MamikDivision of Neurology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Leina B SaitoDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Roobina BoghozianDivision of Neurology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Maria Chiara MonacoNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Eugene O MajorNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Jian-Qiang LuDepartment of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada.
William G BrantonDivision of Neurology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2R3, Canada.
Christopher PowerDepartment of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB T6G 2R3, Canada; chris.power@ualberta.ca.
University of Alberta · CANational Institutes of Health · USWomen and Children’s Health Research Institute · CA

Funding

CIHR
6 · The paper itself

Abstract

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1β and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE). We observed inflammasome activation and pyroptosis in human microglia and ODCs in vitro after exposure to inflammatory stimuli and demonstrate caspase-1 inhibition by the small-molecule inhibitor VX-765 in both cell types. GSDMD inhibition by siRNA transduction suppressed pyroptosis in human microglia. VX-765 treatment of EAE animals reduced the expression of inflammasome- and pyroptosis-associated proteins in the CNS, prevented axonal injury, and improved neurobehavioral performance. Thus, GSDMD-mediated pyroptosis in select glia cells is a previously unrecognized mechanism of inflammatory demyelination and represents a unique therapeutic opportunity for mitigating the disease process in MS and other CNS inflammatory diseases.

Indexed as

Models, BiologicalCaspase 1Caspase InhibitorsCells, CulturedDipeptidesHumansMultiple SclerosisOligodendrogliapara-AminobenzoatesPyroptosisbelnacasanCaspase 1Caspase InhibitorsDipeptidespara-AminobenzoatesEAEgasdermin Dinflammasomemultiple sclerosispyroptosis

Identifiers

PMID29895691
PMCPMC6042136
OpenAlexW2808342347

What OpenQuestion holds

Textmetadata
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.