Evidence map›Paper›PMID 23202730›Full record

ArticleThe Journal of clinical investigation2013

Inhibition of GSK3β-mediated BACE1 expression reduces Alzheimer-associated phenotypes.

Philip T T Ly, Yili Wu, Haiyan Zou, Ruitao Wang, Weihui Zhou, Ayae Kinoshita, Mingming Zhang, Yi Yang, Fang Cai, James Woodgett and 1 more

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

Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 264 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
264citing papers in PubMed, 2 pooled it
12.5field-weighted citation impact, top 1% 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

264 citing papers in PubMed, 2 syntheses or guidelines pooled it, 420 citations in OpenAlex.

  1. Pooled it
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  12. Protein kinases as therapeutic targets in Alzheimer's disease: challenges, insights, and new frontiers.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    Review
  13. Non-microglial downregulation ofbioRxiv : the preprint server for biology · 2026
    Article
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204 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 2 countries.

Philip T T LyTownsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, Vancouver, British Columbia, Canada.
Yili Wu
Haiyan Zou
Ruitao Wang
Weihui Zhou
Ayae Kinoshita
Mingming Zhang
Yi Yang
Fang Cai
James Woodgett
Weihong Song
University of British Columbia · CAKyoto University · JPLunenfeld-Tanenbaum Research Institute · CA

Funding

Canadian Institutes of Health Research MOP-97825Canadian Institutes of Health Research TAD-117948
6 · The paper itself

Abstract

Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the pathological hallmark of Alzheimer's disease (AD). Aβ is generated from sequential cleavages of the β-amyloid precursor protein (APP) by the β- and γ-secretases, and β-site APP-cleaving enzyme 1 (BACE1) is the β-secretase essential for Aβ generation. Previous studies have indicated that glycogen synthase kinase 3 (GSK3) may play a role in APP processing by modulating γ-secretase activity, thereby facilitating Aβ production. There are two highly conserved isoforms of GSK3: GSK3α and GSK3β. We now report that specific inhibition of GSK3β, but not GSK3α, reduced BACE1-mediated cleavage of APP and Aβ production by decreasing BACE1 gene transcription and expression. The regulation of BACE1 gene expression by GSK3β was dependent on NF-κB signaling. Inhibition of GSK3 signaling markedly reduced Aβ deposition and neuritic plaque formation, and rescued memory deficits in the double transgenic AD model mice. These data provide evidence for regulation of BACE1 expression and AD pathogenesis by GSK3β and that inhibition of GSK3 signaling can reduce Aβ neuropathology and alleviate memory deficits in AD model mice. Our study suggests that interventions that specifically target the β-isoform of GSK3 may be a safe and effective approach for treating AD.

Indexed as

Gene Expression Regulation, EnzymologicAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAnimalsAspartic Acid EndopeptidasesDisease Models, AnimalEnzyme ActivationGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHEK293 CellsHumansMiceMice, KnockoutNF-kappa BPlaque, AmyloidAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesAPP protein, humanAspartic Acid EndopeptidasesBACE1 protein, humanBace1 protein, mouseGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, humanGsk3b protein, mouseNF-kappa B

Identifiers

PMID23202730
PMCPMC3533290
OpenAlexW2168597028

What OpenQuestion holds

Textmetadata
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.