Constitutive Nuclear Factor-κB Activity Is Required for Central Neuron Survival
Open accessAbstract
The function of nuclear factor (NF)-kappaB within the developing and mature CNS is controversial. We have generated transgenic mice to reveal NF-kappaB transcriptional activity in vivo. As expected, constitutive NF-kappaB activity was observed within immune organs, and tumor necrosis factor-inducible NF-kappaB activity was present in mesenchymal cells. Intriguingly, NF-kappaB activity was also prominent in the CNS throughout development, especially within neocortex, olfactory bulbs, amygdala, and hippocampus. NF-kappaB in the CNS was restricted to neurons and blocked by overexpression of dominant-negative NF-kappaB-inducible kinase or the IkappaBalphaM super repressor. Blocking endogenous neuronal NF-kappaB activity in cortical neurons using recombinant adenovirus induced neuronal death, whereas induction of NF-kappaB activity increased levels of anti-apoptotic proteins and was strongly neuroprotective. Together, these data demonstrate a physiological role for NF-kappaB in maintaining survival of central neurons.
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PI3K/Akt and NF-κB pathways are critical for CGN survival.
“PI3K/Akt and NF-jB pathways have previously been shown to be critical for CGN survival [37,38].”
From PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling (2012) · cites this paper as [37]
The Results report that blocking NF-κB signaling reduced survival of primary cortical neurons, supporting the NF-κB part of the claim. They do not establish that pathway’s importance specifically in cerebellar granule neurons (CGNs). The paper also does not establish a PI3K/Akt survival effect; that portion may be covered by the other citation in the citing sentence. (LLM, conf=0.86)
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- Authors
- Bhakar, A. L., Tannis, L.-L., Zeindler, C., Russo, M. P., Jobin, C., Park, D. S., MacPherson, S., & Barker, P. A.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- University of North Carolina at Chapel Hill (US)
- University of Ottawa (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2002-10-01
- Volume
- 22
- Issue
- 19
- Pages
- 8466-8475
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6757785
- OpenAlex
- W1767114057
- Cited by
- 310
- References
- 1
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 8 · 2023: 2 · 2022: 6 · 2021: 12 · 2020: 14 · 2019: 10 · 2018: 10 · 2017: 17 · 2016: 12 · 2015: 13 · 2014: 11 · 2013: 18 · 2012: 10
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Killam Trusts
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- NF-κB, neuronal survival, neuroprotection, apoptosis, central nervous system development, neocortex, hippocampus, amygdala, olfactory bulb, adenoviral gene transfer, transgenic mice
- MeSH terms
- NF-kappaB-Inducing Kinase, Animals, beta-Galactosidase, Cell Survival, Cells, Cultured, Central Nervous System, Fibroblasts, Kidney, Luminescent Proteins, Mice, Transgenic, Neurons, Organ Specificity, Transfection, Viral Proteins, Signal Transduction, NF-kappa B, Protein Serine-Threonine Kinases, Genes, Reporter, Proto-Oncogene Proteins c-bcl-2, Green Fluorescent Proteins, bcl-X Protein, Inhibitor of Apoptosis Proteins, Mice, Transcription Factor RelA
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