ArticleThe Journal of biological chemistry2012
Nuclear factor-κB regulates βAPP and β- and γ-secretases differently at physiological and supraphysiological Aβ concentrations.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 72 papers.
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.
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.
Who cites it
72 citing papers in PubMed, 113 citations in OpenAlex.
- NF-κB across the Alzheimer disease spectrum: Context-dependent protective and pathogenic roles.IBRO neuroscience reports · 2026Review
- Glycyrrhizin Ameliorates Learning and Memory Impairment via Inhibition of Neuroinflammation in an Alzheimer's Disease Mouse Model SAMP8.International journal of molecular sciences · 2026Article
- Advances in research on pharmacological mechanisms of anatabine: from nicotinic modulation to multitarget therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- PINK1-dependent NFKB signaling contributes to amyloid pathology in Alzheimer disease.Autophagy · 2025Article
- Cardiovascular Risk Factors, Alzheimer's Disease, and the MIND Diet: A Narrative Review from Molecular Mechanisms to Clinical Outcomes.Nutrients · 2025Review
- The neuroinflammatory role of microRNAs in Alzheimer's disease: pathological insights to therapeutic potential.Molecular and cellular biochemistry · 2025Review
- Fecal Microbiota Transplantation Improves Cognitive Function of a Mouse Model of Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Article
- Review
- The Double-Edged Effects of Substance P in the Pathology of Alzheimer's Disease.Aging and disease · 2024Review
- The regulating effect of curcumin on NF-κB pathway in neurodegenerative diseases: a review of the underlying mechanisms.Inflammopharmacology · 2024Review
- Evaluating the Role of N-Acetyl-L-Tryptophan in the Aβ 1-42-Induced Neuroinflammation and Cognitive Decline in Alzheimer's Disease.Molecular neurobiology · 2024Article
- The roles of RACK1 in the pathogenesis of Alzheimer's disease.Journal of biomedical research · 2024Article
- Potentially PathogenicCells · 2023Article
- Potential drugs for the treatment of Alzheimer's disease.Pharmacological reports : PR · 2023Review
- The Molecular Effects of Environmental Enrichment on Alzheimer's Disease.Molecular neurobiology · 2022Review
- All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease.Neural regeneration research · 2022Review
- Divalent Metal Transporter 1 Knock-Down Modulates IL-1β Mediated Pancreatic Beta-Cell Pro-Apoptotic Signaling Pathways through the Autophagic Machinery.International journal of molecular sciences · 2021Article
- Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target.Journal of biochemical and molecular toxicology · 2021Review
- Interaction of NF-κB and Wnt/β-catenin Signaling Pathways in Alzheimer's Disease and Potential Active Drug Treatments.Neurochemical research · 2021Review
- Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedNuclear factor-κB regulates βAPP and β- and γ-secretases differently at physiological and supraphysiological Aβ concentrations.2015 · Delprete, Dolores [corrected to Del Prete, Dolores]
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Anatomical lesions in Alzheimer disease-affected brains mainly consist of senile plaques, inflammation stigmata, and oxidative stress. The nuclear factor-κB (NF-κB) is a stress-activated transcription factor that is activated around senile plaques. We have assessed whether NF-κB could be differentially regulated at physiological or supraphysiological levels of amyloid β (Aβ) peptides. Under these experimental conditions, we delineated the putative NF-κB-dependent modulation of all cellular participants in Aβ production, namely its precursor βAPP (β-amyloid precursor protein) and the β- and γ-secretases, the two enzymatic machines involved in Aβ genesis. Under physiological conditions, NF-κB lowers the transcriptional activity of the promoters of βAPP, β-secretase (β-site APP-cleaving enzyme 1, BACE1), and of the four protein components (Aph-1, Pen-2, nicastrin, presenilin-1, or presenilin-2) of the γ-secretase in HEK293 cells. This was accompanied by a reduction of both protein levels and enzymatic activities, thereby ultimately yielding lower amounts of Aβ and AICD (APP intracellular domain). In stably transfected Swedish βAPP-expressing HEK293 cells triggering supraphysiological concentrations of Aβ peptides, NF-κB activates the transcription of βAPP, BACE1, and some of the γ-secretase members and increases protein expression and enzymatic activities, resulting in enhanced Aβ production. Our pharmacological approach using distinct NF-κB kinase modulators indicates that both NF-κB canonical and alternative pathways are involved in the control of Aβ production. Overall, our data demonstrate that under physiological conditions, NF-κB triggers a repressive effect on Aβ production that contributes to maintaining its homeostasis, while NF-κB participates in a degenerative cycle where Aβ would feed its own production under pathological conditions.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.