The ubiquitous transcription factor Nuclear Factor-kappa B (NF-kappa B) plays an important role in controlling gene expression in cellular inflammation, immunity, cell proliferation and apoptosis. In mammals, NF-kappa B comprises of a family of five protein subunits, NF-kB1 (p50/p105), NF-kB2 (p52/p100), p65 (RelA), RelB and c-Rel. These NF-kappa B subunits share an N-terminal Rel Homology Domain (RHD) of about 300 amino acid, which contain regions for the dimerization of NF-kappa B subunits, nuclear translocation and DNA binding.
In most unstimulated cells the majority of NF-kappaB subunits, either hetero- or homo-dimers, are retained in an inactive form in the cytoplasm through association with members of a family of inhibitory proteins, known as IkB. IkB proteins all contain an ankyrin repeat of 30-33 amino acids, which can bind the NF-kappa B RHD region. Cellular exposure to a variety of stimuli leads to a rapid phosphorylation, ubiquitination and proteolytic degradation of IkB freeing NF-kappa B dimers to translocate to the nucleus and initiate gene transcription. The degradation of IkB is achieved through the actions of the IkB kinase (IKK) complex. Target gene specificity is determined by the specific NF-kappa B complexes present in different cell types, the kB target site binding specificities of different NF-kappa B complexes and the particular protein-protein interactions and post-translational modifications that NF-kappa B complexes can undergo in different contexts.
Extracellular stimuli that can induce NF-kappa B activation include proinflammatory cytokines (e.g. TNF), bacteria, physiological stress conditions, physical and oxidative stress, environmental factors, therapeutically used drugs, modified proteins, apoptotic mediators, mitogens, growth factors and hormones, and chemical agents, many of which have been implicated in the development of autoimmune and inflammatory diseases.
The reports of the involvement of NF-kappa B in chronic inflammatory diseases have dramatically increased in recent years. Diseases such as, Multiple Sclerosis, Rheumatoid Arthritis, Atherosclerosis, Chronic-inflammatory Demyelinating Polyradiculoneuritis, Asthma, Inflammatory Bowel Disease, Helicobacter pylori -associated gastritis and Systemic Inflammatory Response Syndrome (SIRS).
This research topic aims to explore the effects of the NF-kappa B signalling pathway in the pathogenesis of neurological diseases, and investigate NF-kappa B regulation in context of disease and genetic factors influencing the NF-kappa B pathway. Most importantly it is aimed to foster discussion on NF-kappa B related therapeutic design in neurological diseases. Research work and review articles are all encouraged for submission.
The ubiquitous transcription factor Nuclear Factor-kappa B (NF-kappa B) plays an important role in controlling gene expression in cellular inflammation, immunity, cell proliferation and apoptosis. In mammals, NF-kappa B comprises of a family of five protein subunits, NF-kB1 (p50/p105), NF-kB2 (p52/p100), p65 (RelA), RelB and c-Rel. These NF-kappa B subunits share an N-terminal Rel Homology Domain (RHD) of about 300 amino acid, which contain regions for the dimerization of NF-kappa B subunits, nuclear translocation and DNA binding.
In most unstimulated cells the majority of NF-kappaB subunits, either hetero- or homo-dimers, are retained in an inactive form in the cytoplasm through association with members of a family of inhibitory proteins, known as IkB. IkB proteins all contain an ankyrin repeat of 30-33 amino acids, which can bind the NF-kappa B RHD region. Cellular exposure to a variety of stimuli leads to a rapid phosphorylation, ubiquitination and proteolytic degradation of IkB freeing NF-kappa B dimers to translocate to the nucleus and initiate gene transcription. The degradation of IkB is achieved through the actions of the IkB kinase (IKK) complex. Target gene specificity is determined by the specific NF-kappa B complexes present in different cell types, the kB target site binding specificities of different NF-kappa B complexes and the particular protein-protein interactions and post-translational modifications that NF-kappa B complexes can undergo in different contexts.
Extracellular stimuli that can induce NF-kappa B activation include proinflammatory cytokines (e.g. TNF), bacteria, physiological stress conditions, physical and oxidative stress, environmental factors, therapeutically used drugs, modified proteins, apoptotic mediators, mitogens, growth factors and hormones, and chemical agents, many of which have been implicated in the development of autoimmune and inflammatory diseases.
The reports of the involvement of NF-kappa B in chronic inflammatory diseases have dramatically increased in recent years. Diseases such as, Multiple Sclerosis, Rheumatoid Arthritis, Atherosclerosis, Chronic-inflammatory Demyelinating Polyradiculoneuritis, Asthma, Inflammatory Bowel Disease, Helicobacter pylori -associated gastritis and Systemic Inflammatory Response Syndrome (SIRS).
This research topic aims to explore the effects of the NF-kappa B signalling pathway in the pathogenesis of neurological diseases, and investigate NF-kappa B regulation in context of disease and genetic factors influencing the NF-kappa B pathway. Most importantly it is aimed to foster discussion on NF-kappa B related therapeutic design in neurological diseases. Research work and review articles are all encouraged for submission.
