Evidence map›Paper›PMID 34020681›Full record

ArticleAlzheimer's research & therapy2021

Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model.

Marine Tournissac, Tra-My Vu, Nika Vrabic, Clara Hozer, Cyntia Tremblay, Koralie Mélançon, Emmanuel Planel, Fabien Pifferi, Frédéric Calon

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

Article in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

22 citing papers in PubMed, 32 citations in OpenAlex.

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  11. The βAdvances in pharmacological and pharmaceutical sciences · 2024
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  15. Multisensory Stimulation Reverses Memory Impairment in AdrβInternational journal of molecular sciences · 2023
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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

9 authors at 3 institutions in 2 countries.

Marine TournissacFaculté de pharmacie, Université Laval, 1050 Avenue de la Médecine, Quebec, QC, G1V 0A6, Canada.
Tra-My VuFaculté de pharmacie, Université Laval, 1050 Avenue de la Médecine, Quebec, QC, G1V 0A6, Canada.
Nika VrabicAxe Neurosciences, Centre de recherche du CHU de Québec-Université Laval (Pavillon CHUL), 2705 Boulevard Laurier, Quebec, QC, G1V 4G2, Canada.
Clara HozerUMR CNRS/MNHN 7179, Mécanismes Adaptatifs et Évolution, 1 Avenue du Petit Château, 91800, Brunoy, France.
Cyntia TremblayAxe Neurosciences, Centre de recherche du CHU de Québec-Université Laval (Pavillon CHUL), 2705 Boulevard Laurier, Quebec, QC, G1V 4G2, Canada.
Koralie MélançonFaculté de pharmacie, Université Laval, 1050 Avenue de la Médecine, Quebec, QC, G1V 0A6, Canada.
Emmanuel PlanelAxe Neurosciences, Centre de recherche du CHU de Québec-Université Laval (Pavillon CHUL), 2705 Boulevard Laurier, Quebec, QC, G1V 4G2, Canada.
Fabien PifferiUMR CNRS/MNHN 7179, Mécanismes Adaptatifs et Évolution, 1 Avenue du Petit Château, 91800, Brunoy, France.
Frédéric CalonFaculté de pharmacie, Université Laval, 1050 Avenue de la Médecine, Quebec, QC, G1V 0A6, Canada. frederic.calon@crchul.ulaval.ca.ORCID 0000-0002-4203-0887
Université Laval · CACentre National de la Recherche Scientifique · FRCentre hospitalier de l'Université Laval · CA

Funding

CIHR MOP 102532
6 · The paper itself

Abstract

backgroundOld age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3 adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well.

methodsCL-316,243, a specific β3AR agonist, was administered to the triple transgenic mouse model of AD (3xTg-AD) and non-transgenic controls from 15 to 16 months of age at a dose of 1 mg/kg/day i.p.

resultsHere, we show that β3AR agonist administration decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety, and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice.

conclusionsOverall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.

Indexed as

Alzheimer DiseaseAdrenergic AgonistsAmyloid beta-PeptidesAnimalsDisease Models, AnimalMiceMice, Inbred C57BLMice, Transgenictau ProteinsAdrenergic AgonistsAmyloid beta-Peptidestau Proteins3xTg-AD miceAlzheimer’s diseaseBrown adipose tissueDrug repurposingThermogenesisβ3 adrenergic receptors

Identifiers

PMID34020681
PMCPMC8140479
OpenAlexW3160240799

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.