Abstract
The transcription factor nuclear factor κB (NF-κB) is moving to the forefront of the fields of apoptosis and neuronal plasticity because of recent findings showing that activation of NF-κB prevents neuronal apoptosis in various cell culture and in vivo models and because NF-κB is activated in association with synaptic plasticity. Activation of NF-κB was first shown to mediate antiapoptotic actions of tumor necrosis factor in cultured neurons and was subsequently shown to prevent death of various nonneuronal cells. NF- κB is activated by several cytokines and neurotrophic factors and in response to various cell stressors. Oxidative stress and elevation of intracellular calcium levels are particularly important inducers of NF-κB activation. Activation of NF-κB can interrupt apoptotic biochemical cascades at relatively early steps, before mitochondrial dysfunction and oxyradical production. Gene targets for NF-κB that may mediate its antiapoptotic actions include the antioxidant enzyme manganese superoxide dismutase, members of the inhibitor of apoptosis family of proteins, and the calcium- binding protein calbindin D28k. NF-κB is activated by synaptic activity and may play important roles in the process of learning and memory. The available data identify NF-κB as an important regulator of evolutionarily conserved biochemical and molecular cascades designed to prevent cell death and promote neuronal plasticity. Because NF-κB may play roles in a range of neurological disorders that involve neuronal degeneration and/or perturbed synaptic function, pharmacological and genetic manipulations of NF-κB signaling are being developed that may prove valuable in treating disorders ranging from Alzheimer's disease to schizophrenia.
Original language | English (US) |
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Pages (from-to) | 443-456 |
Number of pages | 14 |
Journal | Journal of Neurochemistry |
Volume | 74 |
Issue number | 2 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
Keywords
- Apoptosis
- Excitotoxicity
- Hippocampus
- Long-term potentiation
- Neurotrophic factor
- Oxidative stress
- Transcription factor
- Tumor necrosis factor
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience