Evidence map›Paper›PMID 25316599›Full record

ArticleNeurobiology of aging2015

Increased Alzheimer's disease-like pathology in the APP/ PS1ΔE9 mouse model lacking Nrf2 through modulation of autophagy.

Gururaj Joshi, Kok Ann Gan, Delinda A Johnson, Jeffrey A Johnson

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

Article in Neurobiology of aging, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

101 citing papers in PubMed, 176 citations in OpenAlex.

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  19. Updates on mouse models of Alzheimer's disease.Molecular neurodegeneration · 2024
    Review
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41 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

4 authors at 1 institution in 1 country.

Gururaj JoshiSchool of Pharmacy, University of Wisconsin-Madison, WI, USA.
Kok Ann GanSchool of Pharmacy, University of Wisconsin-Madison, WI, USA.
Delinda A JohnsonSchool of Pharmacy, University of Wisconsin-Madison, WI, USA; Center of Neuroscience, University of Wisconsin-Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, WI, USA.
Jeffrey A JohnsonSchool of Pharmacy, University of Wisconsin-Madison, WI, USA; Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, WI, USA; Center of Neuroscience, University of Wisconsin-Madison, WI, USA; Waisman Center, University of Wisconsin-Madison, WI, USA. Electronic address: jajohnson@pharmacy.wisc.edu.
University of Wisconsin–Madison · US

Funding

Wisconsin Alzheimer's Disease Research CenterP50AG033514 · NIA · UNIVERSITY OF WISCONSIN-MADISON · PI CHAPPELL, RICHARD J · 2009 to 2018
$16.2M
Transcriptional Control of Antioxidant Genes in BrainR01ES008089 · NIEHS · UNIVERSITY OF WISCONSIN-MADISON · PI JOHNSON, JEFFREY A · 2002 to 2013
$3.7M
NIA NIH HHS P50 AG033514NIA NIH HHS P50AG033514NIEHS NIH HHS R01 ES008089NIEHS NIH HHS R01 ES08089
6 · The paper itself

Abstract

The presence of senile plaques is one of the major pathologic hallmarks of the brain with Alzheimer's disease (AD). The plaques predominantly contain insoluble amyloid β-peptide, a cleavage product of the larger amyloid precursor protein (APP). Two enzymes, named β and γ secretase, generate the neurotoxic amyloid-β peptide from APP. Mature APP is also turned over endogenously by autophagy, more specifically by the endosomal-lysosomal pathway. A defective lysosomal system is known to be pathogenic in AD. Modulation of NF-E2 related factor 2 (Nrf2) has been shown in several neurodegenerative disorders, and Nrf2 has become a potential therapeutic target for various neurodegenerative disorders, including AD, Parkinson's disease, and amyotrophic lateral sclerosis. In the current study, we explored the effect of genetic ablation of Nrf2 on APP/Aβ processing and/or aggregation as well as changes in autophagic dysfunction in APP/PS1 mice. There was a significant increase in inflammatory response in APP/PS1 mice lacking Nrf2. This was accompanied by increased intracellular levels of APP, Aβ (1-42), and Aβ (1-40), without a change total full-length APP. There was a shift of APP and Aβ into the insoluble fraction, as well as increased poly-ubiquitin conjugated proteins in mice lacking Nrf2. APP/PS1-mediated autophagic dysfunction is also enhanced in Nrf2-deficient mice. Finally, neurons in the APP/PS1/Nrf2-/- mice had increased accumulation of multivesicular bodies, endosomes, and lysosomes. These outcomes provide a better understanding of the role of Nrf2 in modulating autophagy in an AD mouse model and may help design better Nrf2 targeted therapeutics that could be efficacious in the treatment of AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsAutophagyDisease Models, AnimalEndosomesGene DeletionLysosomesMice, TransgenicMolecular Targeted TherapyNF-E2-Related Factor 2Amyloid beta-PeptidesAmyloid beta-Protein PrecursorNfe2l2 protein, mouseNF-E2-Related Factor 2Amyloid precursor protein (APP)Amyloid β peptideAutophagymTOR pathwayp62/SQSTM

Identifiers

PMID25316599
PMCPMC4315753
OpenAlexW2071174827

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.