Evidence map›Paper›PMID 29604274›Full record

ArticleBiochemical and biophysical research communications2018

Suppression of tau propagation using an inhibitor that targets the DK-switch of nSMase2.

Tina Bilousova, Chris Elias, Emily Miyoshi, Mohammad Parvez Alam, Chunni Zhu, Jesus Campagna, Kanagasabai Vadivel, Barbara Jagodzinska, Karen Hoppens Gylys, Varghese John

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemical and biophysical research communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
    Review
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  6. Article
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  9. Article
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  11. Review
  12. Article
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  14. Mechanisms of secretion and spreading of pathological tau protein.Cellular and molecular life sciences : CMLS · 2020
    Review
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  16. Review
  17. Review
  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

10 authors.

Tina BilousovaDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA; Gylys Lab, School of Nursing, University of California, Los Angeles, CA, USA.
Chris EliasDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA.
Emily MiyoshiGylys Lab, School of Nursing, University of California, Los Angeles, CA, USA.
Mohammad Parvez AlamDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA.
Chunni ZhuDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA.
Jesus CampagnaDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA.
Kanagasabai VadivelDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA.
Barbara JagodzinskaDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA.
Karen Hoppens GylysGylys Lab, School of Nursing, University of California, Los Angeles, CA, USA.
Varghese JohnDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, USA. Electronic address: vjohn@mednet.ucla.edu.

Funding

ApoE4-targeted therapeutics that normalize SirT1R01AG051386 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JOHN, VARGHESE · 2015 to 2019
$3.0M
NIA NIH HHS R01 AG051386
6 · The paper itself

Abstract

Targeting of molecular pathways involved in the cell-to-cell propagation of pathological tau species is a novel approach for development of disease-modifying therapies that could block tau pathology and attenuate cognitive decline in patients with Alzheimer's disease and other tauopathies. We discovered cambinol through a screening effort and show that it is an inhibitor of cell-to-cell tau propagation. Our in vitro data demonstrate that cambinol inhibits neutral sphingomyelinase 2 (nSMase2) enzyme activity in dose response fashion, and suppresses extracellular vesicle (EV) production while reducing tau seed propagation. Our in vivo testing with cambinol shows that it can reduce the nSMase2 activity in the brain after oral administration. Our molecular docking and simulation analysis reveals that cambinol can target the DK-switch in the nSMase2 active site.

Indexed as

AnimalsBiosensing TechniquesBrainCell-Free SystemEnzyme InhibitorsExtracellular VesiclesHEK293 CellsHumansMice, Inbred C57BLModels, MolecularNaphthalenesPermeabilityProtein DomainsPyrimidinonesSphingomyelin Phosphodiesterasetau ProteinscambinolEnzyme InhibitorsNaphthalenesPyrimidinonesSMPD3 protein, humanSmpd3 protein, mouseSphingomyelin Phosphodiesterasetau ProteinsTissue ExtractsCambinolExtracellular vesiclesMolecular modelingnSMase2Tau biosensorTauopathy

Identifiers

PMID29604274
PMCPMC5956110

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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.