Evidence map›Paper›PMID 30300917›Full record

ArticleJournal of neurochemistry2019

Wnt-induced activation of glucose metabolism mediates the in vivo neuroprotective roles of Wnt signaling in Alzheimer disease.

Pedro Cisternas, Juan M Zolezzi, Milka Martinez, Viviana I Torres, Guang William Wong, Nibaldo C Inestrosa

Open access · bronzeAbstract read
In one paragraph

Article in Journal of neurochemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 66 citations in OpenAlex.

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  20. Neurobiological Promises of the Bitter Diterpene Lactone Andrographolide.Oxidative medicine and cellular longevity · 2022
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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

6 authors at 2 institutions in 3 countries.

Pedro CisternasDepartamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.
Juan M ZolezziDepartamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.
Milka MartinezDepartamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.
Viviana I TorresDepartamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.
Guang William WongDepartment of Physiology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nibaldo C InestrosaDepartamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración (CARE-UC), Pontificia Universidad Católica de Chile, Santiago, Chile.ORCID 0000-0002-7084-0318
Pontificia Universidad Católica de Chile · CLJohns Hopkins University · US

Funding

CTRP and Metabolic ControlR01DK084171 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI Guang William Wong · 2010 to 2026
$8.0M
NIDDK NIH HHS R01 DK084171
6 · The paper itself

Abstract

Dysregulated Wnt signaling is linked to major neurodegenerative diseases, including Alzheimer disease (AD). In mouse models of AD, activation of the canonical Wnt signaling pathway improves learning/memory, but the mechanism for this remains unclear. The decline in brain function in AD patients correlates with reduced glucose utilization by neurons. Here, we test whether improvements in glucose metabolism mediate the neuroprotective effects of Wnt in AD mouse model. APPswe/PS1dE9 transgenic mice were used to model AD, Andrographolide or Lithium was used to activate Wnt signaling, and cytochalasin B was used to block glucose uptake. Cognitive function was assessed by novel object recognition and memory flexibility tests. Glucose uptake and the glycolytic rate were determined using radiotracer glucose. The activities of key enzymes of glycolysis such as hexokinase and phosphofructokinase, Adenosine triphosphate (ATP)/Adenosine diphosphate (ADP) levels and the pentose phosphate pathway and activity of glucose-6 phosphate dehydrogenase were measured. Wnt activators significantly improved brain glucose utilization and cognitive performance in transgenic mice. Wnt signaling enhanced glucose metabolism by increasing the expression and/or activity of hexokinase, phosphofructokinase and AMP-activated protein kinase. Inhibiting glucose uptake partially abolished the beneficial effects of Wnt signaling on learning/memory. Wnt activation also enhanced glucose metabolism in cortical and hippocampal neurons, as well as brain slices derived from APPswe/PS1E9 transgenic mice. Combined, these data provide evidence that the neuroprotective effects of Wnt signaling in AD mouse models result, at least in part, from Wnt-mediated improvements in neuronal glucose metabolism.

Indexed as

Alzheimer DiseaseAnimalsBrainGlucoseHumansMiceMice, TransgenicRatsWnt Signaling PathwayGlucoseAlzheimer diseaseglucose metabolismneuroprotectionWnt signaling

Identifiers

PMID30300917
PMCPMC7680578
OpenAlexW2897107688

What OpenQuestion holds

Textmetadata
LicenceTDM
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.