Evidence map›Paper›PMID 33803482›Full record

ArticleInternational journal of molecular sciences2021

The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice.

Johanna Michael, Julia Zirknitzer, Michael Stefan Unger, Rodolphe Poupardin, Tanja Rieß, Nadine Paiement, Horst Zerbe, Birgit Hutter-Paier, Herbert Reitsamer, Ludwig Aigner

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.

  1. Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review.European respiratory review : an official journal of the European Respiratory Society · 2023
    Pooled it
  2. Article
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  8. CysLTJournal of neurochemistry · 2025
    Article
  9. Montelukast alleviates neuroinflammation and improves motor functions in the line 61 model of Parkinson's disease: An exploratory study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  10. Article
  11. Immune modulation to treat Alzheimer's disease.Molecular neurodegeneration · 2025
    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

10 authors at 2 institutions in 1 country.

Johanna MichaelInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
Julia ZirknitzerInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
Michael Stefan UngerInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
Rodolphe PoupardinSpinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, 5020 Salzburg, Austria.
Tanja RießInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
Nadine PaiementIntelgenX Corp., Saint-Laurent, QC H4S 1Y2, Canada.
Horst ZerbeIntelgenX Corp., Saint-Laurent, QC H4S 1Y2, Canada.
Birgit Hutter-PaierQPS Neuropharmacology, 8074 Grambach/Graz, Austria.
Herbert ReitsamerResearch Program for Experimental Ophthalmology, Department of Ophthalmology and Optometry, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria.
Ludwig AignerInstitute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria.
Paracelsus Medical University · ATQPS (Austria) · AT

Funding

Austrian Science Fund P 31362-B34Austrian Science Fund FWF P 31362
6 · The paper itself

Abstract

Alzheimer's disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. In consequence, leukotriene signaling-more specifically, the leukotriene receptors-has been recognized as a potential drug target to ameliorate AD pathology. Here, we analyzed the effects of the leukotriene receptor antagonist montelukast (MTK) on hippocampal gene expression in 5xFAD mice, a commonly used transgenic AD mouse model. We identified glial activation and neuroinflammation as the main pathways modulated by MTK. The treatment increased the number of Tmem119+ microglia and downregulated genes related to AD-associated microglia and to lipid droplet-accumulating microglia, suggesting that the MTK treatment targets and modulates microglia phenotypes in the disease model compared to the vehicle. MTK treatment further reduced infiltration of CD8+T-cells into the brain parenchyma. Finally, MTK treatment resulted in improved cognitive functions. In summary, we provide a proof of concept for MTK to be a potential drug candidate for AD and provide novel modes of action via modulation of microglia and CD8+ T-cells. Of note, 5xFAD females showed a more severe pathology, and in consequence, MTK treatment had a more pronounced effect in the females compared to the males. The effects on neuroinflammation, i.e., microglia and CD8+ T-cells, as well as the effects on cognitive outcome, were dose-dependent, therefore arguing for the use of higher doses of MTK in AD clinical trials compared to the approved asthma dose.

Indexed as

AcetatesAlzheimer DiseaseAnimalsBrainCD8-Positive T-LymphocytesCognitionCyclopropanesInflammationLeukotriene AntagonistsMiceMice, TransgenicQuinolinesSulfidesAcetatesCyclopropanesLeukotriene AntagonistsmontelukastQuinolinesSulfides5xFADAlzheimer’s diseasecognitioncysteinyl leukotrienesleukotriene receptor antagonistmicrogliamontelukastRNAseq

Identifiers

PMID33803482
PMCPMC7967180
OpenAlexW3133591222

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.