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Cited by 877NF-κB Signaling PathwaysNeuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology Research

NF-κB in neuronal plasticity and neurodegenerative disorders

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Mattson, Mark P., Camandola, Simonetta·2001·Journal of Clinical Investigation
DOI 10.1172/jci11916PMC PMC199201
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Abstract

NF-κB in defense and diseaseNF-κB is widely known for its ubiquitous roles in inflammation and immune responses, as well as in control of cell division and apoptosis.These roles are apparent in the nervous system, but neurons and their neighboring cells employ the NF-κB pathway for distinctive functions as well, ranging from development to the coordination of cellular responses to injury of the nervous system and to brain-specific processes such as the synaptic signaling that underlies learning and memory.Here we discuss the regulation of NF-κB activity by neurotransmitters and neurotrophic factors and the physiological and pathological effects of NF-κB activation in neurons and glial cells.Based on work in animal models, it appears that manipulation of NF-κB signaling may prove valuable in treating such conditions as ischemic stroke, physical trauma to the brain or spinal cord, and neurodegenerative disorders, including Alzheimer's disease and Parkinson's disease. NF-κB in the nervous system: what, when, and whereThe molecular composition of NF-κB DNA-binding dimers, and the proteins that modulate the activation and function of NF-κB, have been reviewed previously (1).As in other organ systems, functional NF-κB complexes are present in essentially all cell types in the nervous system, including neurons, astrocytes, microglia, and oligodendrocytes (2).The most common subunits expressed are p50, p65, and IκBα.In addition, novel and developmentally regulated NF-κB subunits may be expressed in the nervous system, including a recently described neuronal κB factor (3). Receptor-linked signal transduction pathways that ultimately result in NF-κB activation, such as those activated by TNF-α and Fas ligand, have also been documented in neurons and glial cells (4).Additional neuron-specific signals that activate NF-κB include nerve growth factor (NGF) (5) and the secreted form of β-amyloid precursor protein (βAPP) (Figure 1) (6).A major pathway leading to NF-κB activation involves IκB phosphorylation by IκB kinase (IKK), which consists of two catalytic subunits (IKK-α and IKK-β) and a regulatory subunit called IKK-γ.Neural cells express NF-κB in development and plasticity of the nervous system Many of the same signal transduction pathways that regulate neuronal survival and growth during development of the nervous system appear to be centrally involved in various neurodegenerative conditions.Knowledge gained from studies of the function of NF-κB in developing neurons is therefore likely to be relevant to the pathogenesis of neurological disorders.An evolutionarily conserved role for NF-κB in development is suggested by data showing that the NF-κB in neuronal plasticity and neurodegenerative disorders

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  • Overexpression of BDNF may lead to an inflammatory response mediated by NF-κB, leading to astrocyte activation, increased production of cytokines and neurotoxic reactive oxygen species, and local recruitment of activated microglia.

    “It is possible that overexpression of BDNF leads to an inflammatory response mediated by NF-κB, leading to astrocyte activation, increased production of cytokines and neurotoxic reactive oxygen species, and local recruitment of activated microglia [193].”

    From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [193]

  • Activation of NF-κB plays a pivotal role in the activation of astrocytes and their production of TNFα and other pro-inflammatory cytokines.

    “activation of NF-κB plays a pivotal role in the activation of astrocytes and their production of TNFα and other pro-inflammatory cytokines (O’Neill et al., 1997; Mattson et al., 2001).”

    From Evidence for miR‐181 involvement in neuroinflammatory responses of astrocytes (2013) · cites this paper as Mattson et al., 2001

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  1. Barger, S.W., et al. 1995. Tumor necrosis factors α and β protect neu- rons against amyloid β-peptide toxicity: evidence for involvement of a κB-binding factor and attenuation of peroxide and Ca 2+ accumula- tion. Proc. Natl. Acad. Sci. USA. 92:9328-9332.

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Authors
Mattson, M. P., & Camandola, S.
Affiliations
National Institutes of Health (US)
Corresponding author
Mattson, Mark P.
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2001-02-01
Volume
107
Issue
3
Pages
247-254
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci11916
PMC
PMC199201
OpenAlex
W1964780858
Cited by
877
References
37
Citations by year
2026: 18 · 2025: 21 · 2024: 23 · 2023: 27 · 2022: 35 · 2021: 44 · 2020: 33 · 2019: 19 · 2018: 25 · 2017: 31 · 2016: 34 · 2015: 42 · 2014: 39 · 2013: 34 · 2012: 26
FWCI
3.63
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
neuroplasticity, neurodegenerative diseases, neuroinflammation, IκB kinase, IκB phosphorylation, neurotrophic factors, neurotransmitters, nerve growth factor, amyloid precursor protein, Alzheimer's disease, Parkinson's disease, ischemic stroke, traumatic brain injury, spinal cord injury, glial cells, synaptic signaling
MeSH terms
Alzheimer Disease, Animals, Brain Injuries, Brain Ischemia, Chronic Disease, Electric Stimulation, Gene Expression Regulation, Humans, Nervous System, Neuronal Plasticity, Neurons, Seizures, Signal Transduction, NF-kappa B, Apoptosis, Microglia, Neurotransmitter Agents, Neurodegenerative Diseases

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