Free Radicals, Calcium., and The Synaptic Plasticity-Cell Death Continuum: Emerging Roles of The Transcription Factor Nfκb

Abstract

Publisher Summary Neurotransmitters, neurotrophic factors, cytokines, and cell adhesion molecules are among the categories of intercellular signals that play major roles in regulating neurite outgrowth, synaptogenesis, and synaptic plasticity. The central role of calcium and oxy radicals in orchestrating various adaptive responses of neurons probably arises from the fact that multicellular organisms evolved in an oxidizing environment and under conditions of ionic turmoil. Calcium influx regulates growth cone behavior by controlling the state of polymerization of microfilaments and microtubules, the cytoskeletal underpinnings of filipodial movements and neurite elongation, respectively. Learning and memory are encoded by signaling processes initiated at synapses that are transduced into long-term changes in neuronal excitability. Induction of gene expression appears to be involved in maintenance of the strengthening of synaptic connections in paradigms of learning and memory. Research findings suggest that the NF K B plays an important role in transducing calcium and ROS synaptic signals into genetic responses. NF K B is a cytosolic transcription factor that can be activated in response to synaptic activity. This provides a mechanism of synapse-to-nucleus signaling that plays an important role in activity-dependent long-lasting changes in neuronal structure and function. NF K B also appears to play an important role in the adaptive responses of neurons to potentially lethal excitotoxic, metabolic, and oxidative insults. NF K B induces the expression of genes encoding cytoprotective proteins, including those that suppress the accumulation of ROS, for example, manganese superoxide dismutase, and stabilize calcium homeostasis, for example the calcium-binding protein calbindin.