Evidence map›Paper›PMID 39498012›Full record

ArticleHeliyon2024

Pharmacological inhibition of PLK2 kinase activity mitigates cognitive decline but aggravates APP pathology in a sex-dependent manner in APP/PS1 mouse model of Alzheimer's disease.

Laura Martínez-Drudis, Morgan Bérard, Dylan Musiol, Serge Rivest, Abid Oueslati

Abstract read
In one paragraph

Article in Heliyon, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. 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

5 authors.

Laura Martínez-DrudisCHU de Québec-Université Laval Research Center, Neuroscience Axis, 2705 Boulevard Laurier, Quebec City, Canada.
Morgan BérardCHU de Québec-Université Laval Research Center, Neuroscience Axis, 2705 Boulevard Laurier, Quebec City, Canada.
Dylan MusiolCHU de Québec-Université Laval Research Center, Neuroscience Axis, 2705 Boulevard Laurier, Quebec City, Canada.
Serge RivestCHU de Québec-Université Laval Research Center, Neuroscience Axis, 2705 Boulevard Laurier, Quebec City, Canada.
Abid OueslatiCHU de Québec-Université Laval Research Center, Neuroscience Axis, 2705 Boulevard Laurier, Quebec City, Canada.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Converging evidence from clinical and experimental studies suggest the potential significance of Polo-like kinase 2 (PLK2) in regulating the phosphorylation and toxicity of the Alzheimer's disease (AD)-related protein, amyloid precursor protein (APP). These findings have prompted various experimental trials aimed at inhibiting PLK2 kinase activity in different transgenic mouse models of AD. While positive impacts on cognitive decline were reported in these studies, the cellular effects remained controversial. In the present study, we sought to assess the cognitive and cellular consequences of chronic PLK2 inhibitor treatment in the APP/PS1 transgenic mouse model of AD. First, we confirmed that inhibiting PLK2 prevented cognitive decline in a sex-dependent manner, particularly by enhancing working memory in male APP/PS1 mice. Surprisingly, cellular analysis revealed that treatment with PLK2 inhibitor increased the load of amyloid plaques and elevated levels of soluble amyloid β (Aβ) 40 and Aβ42 in the cortex, as well as insoluble Aβ42 in the hippocampus of female mice, without affecting APP pathology in males. These results underscore the potential of PLK2 inhibition to mitigate cognitive symptoms in males. However, paradoxically, it intensifies amyloid pathology in females by enhancing APP amyloidogenic processing, creating a controversial aspect to its therapeutic impact. Overall, these data highlight the sex-dependent nature of the effects of PLK2 inhibition, which may also be influenced by the genetic background of the transgenic mouse model utilized.

Indexed as

Alzheimer's diseaseAmyloid βAPP/PS1 mouse modelPolo-like kinase 2Sex dimorphism

Identifiers

PMID39498012
PMCPMC11532864

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.