Evidence map›Paper›PMID 36297501›Full record

ArticlePharmaceutics2022

Dendrimer-Conjugated nSMase2 Inhibitor Reduces Tau Propagation in Mice.

Carolyn Tallon, Benjamin J Bell, Anjali Sharma, Arindom Pal, Medhinee M Malvankar, Ajit G Thomas, Seung-Wan Yoo, Kristen R Hollinger, Kaleem Coleman, Elizabeth L Wilkinson and 5 more

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

Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

12 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Review
  3. Inhibition of microglial glutaminase alleviates chronic stress-induced neurobehavioral and cognitive deficits.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  4. Nanoparticles as an Encouraging Therapeutic Approach to Alzheimer's Disease.International journal of molecular sciences · 2025
    Review
  5. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
    Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. 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

15 authors at 2 institutions in 1 country.

Carolyn TallonJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.ORCID 0000-0003-4888-547X
Benjamin J BellJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
Anjali SharmaCenter for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Arindom PalJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
Medhinee M MalvankarJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
Ajit G ThomasJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
Seung-Wan YooDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Kristen R HollingerJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
Kaleem ColemanJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.
Elizabeth L WilkinsonCenter for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Sujatha KannanCenter for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Norman J HaugheyDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Rangaramanujam M KannanCenter for Nanomedicine, Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Rana RaisJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.ORCID 0000-0003-4059-2453
Barbara S SlusherJohns Hopkins Drug Discovery, Baltimore, MD 21205, USA.ORCID 0000-0001-9814-4157
Johns Hopkins University · USKennedy Krieger Institute · US

Funding

Therapeutic CoreP30MH075673 · NIMH · JOHNS HOPKINS UNIVERSITY · PI Leah Helane Rubin · 2006 to 2026
$33.2M
HopkinsPREP: Research, Community, Professional Training and Personal GrowthR25GM109441 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI WILSON, KATHERINE L · 2015 to 2024
$3.2M
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
Alzheimer's Association T-PEP-18-579974CNIA NIH HHS R01 AG059799NIA NIH HHS R01 AG063831NIGMS NIH HHS R25 GM109441NIH HHS P30 MH075673NIH HHS R01 AG059799NIH HHS R01 AG063831NIH HHS R25 GM109441NIMH NIH HHS P30 MH075673
6 · The paper itself

Abstract

Alzheimer's disease (AD) is characterized by the progressive accumulation of amyloid-β and hyperphosphorylated tau (pTau), which can spread throughout the brain via extracellular vesicles (EVs). Membrane ceramide enrichment regulated by the enzyme neutral sphingomyelinase 2 (nSMase2) is a critical component of at least one EV biogenesis pathway. Our group recently identified 2,6-Dimethoxy-4-(5-Phenyl-4-Thiophen-2-yl-1H-Imidazol-2-yl)-Phenol (DPTIP), the most potent (30 nM) and selective inhibitor of nSMase2 reported to date. However, DPTIP exhibits poor oral pharmacokinetics (PK), modest brain penetration, and rapid clearance, limiting its clinical translation. To enhance its PK properties, we conjugated DPTIP to a hydroxyl-PAMAM dendrimer delivery system, creating dendrimer-DPTIP (D-DPTIP). In an acute brain injury model, orally administered D-DPTIP significantly reduced the intra-striatal IL-1β-induced increase in plasma EVs up to 72 h post-dose, while oral DPTIP had a limited effect. In a mouse tau propagation model, where a mutant hTau (P301L/S320F) containing adeno-associated virus was unilaterally seeded into the hippocampus, oral D-DPTIP (dosed 3× weekly) significantly inhibited brain nSMase2 activity and blocked the spread of pTau to the contralateral hippocampus. These data demonstrate that dendrimer conjugation of DPTIP improves its PK properties, resulting in significant inhibition of EV propagation of pTau in mice. Dendrimer-based delivery of DPTIP has the potential to be an exciting new therapeutic for AD.

Indexed as

Alzheimer’s diseaseceramidedendrimerDPTIPextracellular vesiclesneutral sphingomyelinase 2PDDCtau

Identifiers

PMID36297501
PMCPMC9609094
OpenAlexW4297522412

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.