The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer's disease
Open accessAbstract
Elevated levels of β-site APP cleaving enzyme 1 (BACE1) were found in the brain of some sporadic Alzheimer's disease (AD) patients; however, the underlying mechanism is unknown. BACE1 cleaves β-amyloid precursor protein (APP) to generate amyloid β protein (Aβ), a central component of neuritic plaques in AD brains. Nuclear factor-kappa B (NF-κB) signalling plays an important role in gene regulation and is implicated in inflammation, oxidative stress and apoptosis. In this report we found that both BACE1 and NF-κB p65 levels were significantly increased in the brains of AD patients. Two functional NF-κB-binding elements were identified in the human BACE1 promoter region. We found that NF-κB p65 expression resulted in increased BACE1 promoter activity and BACE1 transcription, while disruption of NF-κB p65 decreased BACE1 gene expression in p65 knockout (RelA-knockout) cells. In addition, NF-κB p65 expression leads to up-regulated β-secretase cleavage and Aβ production, while non-steroidal anti-inflammatory drugs (NSAIDs) inhibited BACE1 transcriptional activation induced by strong NF-κB activator tumour necrosis factor-alpha (TNF-α). Taken together, our results clearly demonstrate that NF-κB signalling facilitates BACE1 gene expression and APP processing, and increased BACE1 expression mediated by NF-κB signalling in the brain could be one of the novel molecular mechanisms underlying the development of AD in some sporadic cases. Furthermore, NSAIDs could block the inflammation-induced BACE1 transcription and Aβ production. Our study suggests that inhibition of NF-κB-mediated BACE1 expression may be a valuable drug target for AD therapy.
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“Furthermore, treatment with non‐steroidal anti‐inflammatory drugs (NSAIDs) was found to decrease BACE1 transcription and subsequent production of Aβ.”
From BACE1: More than just a β‐secretase (2022) · cites this paper as [152]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“The BACE1 promotor has an NFκB binding site. When phosphorylated, NFκB increases BACE1 promotor activity and transcription.”
From BACE1: More than just a β‐secretase (2022) · cites this paper as [152]
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“Moreover, it has also been proposed as a molecular factor underlying some sporadic forms of AD (Chen et al., 2012).”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Chen et al., 2012
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A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity
Weggen, S., Eriksen, J. L., Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., et al. (2001) · Nature · doi:10.1038/35102591 · Cited by 1,388
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Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066
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Glycogen synthase kinase-3 signaling in Alzheimer’s disease
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Metadata
- Authors
- Chen, C.-H., Zhou, W., Liu, S., Deng, Y., Cai, F., Tone, M., Tone, Y., Tong, Y., & Song, W.
- Affiliations
- University of British Columbia (CA)
- University of Pennsylvania (US)
- Corresponding author
- Song, Weihong
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-02-18
- Volume
- 15
- Issue
- 01
- Pages
- 77-90
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2158215064
- Cited by
- 433
- References
- 41
- Citations by year
- 2026: 33 · 2025: 55 · 2024: 51 · 2023: 39 · 2022: 40 · 2021: 26 · 2020: 47 · 2019: 25 · 2018: 25 · 2017: 18 · 2016: 20 · 2015: 17 · 2014: 12 · 2013: 11 · 2012: 6
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Michael Smith Health Research BC
- Canada Research Chairs
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, BACE1, NF-κB signaling, NF-κB p65, beta-secretase, amyloid-beta production, APP processing, transcriptional regulation, nonsteroidal anti-inflammatory drugs, TNF-α, inflammation, therapeutic target
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Anti-Inflammatory Agents, Non-Steroidal, Brain, Humans, Promoter Regions, Genetic, Transcription, Genetic, Tumor Necrosis Factor-alpha, Signal Transduction, Up-Regulation, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Transcription Factor RelA, Amyloid Precursor Protein Secretases
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