Evidence map›Paper›PMID 34678224›Full record

ArticleBiochemical pharmacology2021

Inhibition of neutral sphingomyelinase 2 reduces extracellular vesicle release from neurons, oligodendrocytes, and activated microglial cells following acute brain injury.

Carolyn Tallon, Silvia Picciolini, Seung-Wan Yoo, Ajit G Thomas, Arindom Pal, Jesse Alt, Cristiano Carlomagno, Alice Gualerzi, Rana Rais, Norman J Haughey and 2 more

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

Article in Biochemical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.6field-weighted citation impact, top 9% 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, 38 citations in OpenAlex.

  1. Article
  2. Review
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  6. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
    Review
  7. Article
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  11. Review
  12. Article
  13. Article
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  16. Inhibition of neutral sphingomyelinase 2 impairs HIV-1 envelope formation and substantially delays or eliminates viral rebound.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  17. Article
  18. Article
  19. 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

12 authors at 3 institutions in 2 countries.

Carolyn TallonJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Silvia PiccioliniIRCCS Fondazione Don Carlo Gnocchi ONLUS, Laboratory of Nanomedicine and Clinical Biophotonics (LABION), Milan, Italy.
Seung-Wan YooDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Ajit G ThomasJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Arindom PalJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Jesse AltJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Cristiano CarlomagnoIRCCS Fondazione Don Carlo Gnocchi ONLUS, Laboratory of Nanomedicine and Clinical Biophotonics (LABION), Milan, Italy.
Alice GualerziIRCCS Fondazione Don Carlo Gnocchi ONLUS, Laboratory of Nanomedicine and Clinical Biophotonics (LABION), Milan, Italy.
Rana RaisJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Norman J HaugheyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Marzia BedoniIRCCS Fondazione Don Carlo Gnocchi ONLUS, Laboratory of Nanomedicine and Clinical Biophotonics (LABION), Milan, Italy. Electronic address: mbedoni@dongnocchi.it.
Barbara S SlusherJohns Hopkins Drug Discovery, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: bslusher@jhmi.edu.
Don Carlo Gnocchi Foundation · ITJohns Hopkins Medicine · USJohns Hopkins University · US

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Barbara Stauch Slusher · 2006 to 2026
$33.2M
Regulation of Exosome Secretion as a novel therapeutic approach for Alzheimer's DiseaseR01AG059799 · NIA · JOHNS HOPKINS UNIVERSITY · PI SLUSHER, BARBARA STAUCH, TSUKAMOTO, TAKASHI · 2018 to 2022
$2.4M
Dendrimer-conjugated nSMase2 inhibitor as a novel therapeutic approach for Alzheimer's DiseaseR01AG063831 · NIA · JOHNS HOPKINS UNIVERSITY · PI RAIS, RANA, RANGARAMANUJAM, KANNAN · 2020 to 2024
$2.3M
NIA NIH HHS R01 AG059799NIA NIH HHS R01 AG063831NIMH NIH HHS P30 MH075673
6 · The paper itself

Abstract

Extracellular Vesicles (EVs) are implicated in the spread of pathogenic proteinsin a growing number of neurological diseases. Given this, there is rising interest in developing inhibitors of Neutral Sphingomyelinase 2 (nSMase2), an enzyme critical in EV biogenesis. Our group recently discovered phenyl(R)-(1-(3-(3,4-dimethoxyphenyl)-2,6-dimethylimidazo[1,2-b]pyridazin-8-yl)pyrrolidin-3-yl)carbamate (PDDC), the first potent, selective, orally-available, and brain-penetrable nSMase2 inhibitor, capable of dose-dependently reducing EVs release in vitro and in vivo. Herein, using multiplexed Surface Plasmon Resonance imaging (SPRi), we evaluated which brain cell-derived EVs were affected by PDDC following acute brain injury. Mice were fed PDDC-containing chow at doses which gave steady PDDC brain exposures exceeding its nSMase2 IC

Indexed as

AnimalsBrain InjuriesCarnitineCorpus StriatumExtracellular VesiclesInjections, IntraventricularInterleukin-1betaMaleMiceMice, TransgenicMicrogliaNeuronsOligodendrogliaPyrenesSphingomyelin PhosphodiesteraseCarnitineIL1B protein, mouseInterleukin-1betapyrenedodecanoylcarnitinePyrenesSmpd3 protein, mouseSphingomyelin PhosphodiesteraseExosomesExtracellular vesiclesMicrogliaNeuroinflammationNeutral sphingomyelinase 2Surface plasmon resonance imaging

Identifiers

PMID34678224
PMCPMC8919377
OpenAlexW3205685091

What OpenQuestion holds

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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.