13
views
0
recommends
+1 Recommend
1 collections
    0
    shares

      To submit to Bentham Journals, please click here

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Role of Nuclear Factor Kappa B (NF-KB) Signalling in Neurodegenerative Diseases: An Mechanistic Approach

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          A transcriptional regulatory nuclear factor kappa B (NF-KB) protein is a modulator of cellular biological activity via binding to a promoter region in the nucleus and transcribing various protein genes. The recent research implicated the intensive role of nuclear factor kappa B (NF-KB) in diseases like autoimmune disorder, inflammatory, cardiovascular and neurodegenerative diseases. Therefore, targeting the nuclear factor kappa B (NF-KB) protein offers a new opportunity as a therapeutic approach. Activation of IKB kinase/NF-KB signaling pathway leads to the development of various pathological conditions in human beings, such as neurodegenerative, inflammatory disorders, autoimmune diseases, and cancer. Therefore, the transcriptional activity of IKB kinase/NF-KB is strongly regulated at various cascade pathways. The nuclear factor NF-kB pathway plays a major role in the expression of pro-inflammatory genes, including cytokines, chemokines, and adhesion molecules. In response to the diverse stimuli, the cytosolic sequestered NF-KB in an inactivated form by binding with an inhibitor molecule protein (IkB) gets phosphorylated and translocated into the nucleus further transcribing various genes necessary for modifying various cellular functions. The various researches confirmed the role of different family member proteins of NF-KB implicated in expressing various genes products and mediating various cellular cascades. MicroRNAs, as regulators of NF- KB microRNAs play important roles in the regulation of the inflammatory process. Therefore, the inhibitor of NF-KB and its family members plays a novel therapeutic target in preventing various diseases. Regulation of NF- KB signaling pathway may be a safe and effective treatment strategy for various disorders.

          Related collections

          Most cited references231

          • Record: found
          • Abstract: found
          • Article: not found

          Neuroinflammation in Alzheimer's disease.

          Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The NF-kappaB family of transcription factors and its regulation.

            Nuclear factor-kappaB (NF-kappaB) consists of a family of transcription factors that play critical roles in inflammation, immunity, cell proliferation, differentiation, and survival. Inducible NF-kappaB activation depends on phosphorylation-induced proteosomal degradation of the inhibitor of NF-kappaB proteins (IkappaBs), which retain inactive NF-kappaB dimers in the cytosol in unstimulated cells. The majority of the diverse signaling pathways that lead to NF-kappaB activation converge on the IkappaB kinase (IKK) complex, which is responsible for IkappaB phosphorylation and is essential for signal transduction to NF-kappaB. Additional regulation of NF-kappaB activity is achieved through various post-translational modifications of the core components of the NF-kappaB signaling pathways. In addition to cytosolic modifications of IKK and IkappaB proteins, as well as other pathway-specific mediators, the transcription factors are themselves extensively modified. Tremendous progress has been made over the last two decades in unraveling the elaborate regulatory networks that control the NF-kappaB response. This has made the NF-kappaB pathway a paradigm for understanding general principles of signal transduction and gene regulation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Mechanisms underlying inflammation in neurodegeneration.

              Inflammation is associated with many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. In this Review, we discuss inducers, sensors, transducers, and effectors of neuroinflammation that contribute to neuronal dysfunction and death. Although inducers of inflammation may be generated in a disease-specific manner, there is evidence for a remarkable convergence in the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators. A major unanswered question is whether pharmacological inhibition of inflammation pathways will be able to safely reverse or slow the course of disease. 2010 Elsevier Inc. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                October 2020
                October 2020
                : 18
                : 10
                : 918-935
                Affiliations
                [1 ]Chitkara College of Pharmacy, Chitkara University, Punjab, India
                Author notes
                [* ]Address correspondence to this author at the Chitkara College of Pharmacy, Chitkara University, Punjab, India; Tel: +919815951171; Fax: 01763503870; E-mails: gurjeet.singh@ 123456chitkara.edu.in , gurjeetthakur@ 123456gmail.com
                Article
                CN-18-918
                10.2174/1570159X18666200207120949
                7709146
                32031074
                8f24ee21-a1dd-42dc-ac88-a7de8e7f9c29
                © 2020 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 08 January 2020
                : 05 February 2020
                : 05 February 2020
                Categories
                Article

                Pharmacology & Pharmaceutical medicine
                transcriptional,nuclear factor kappa b (nf-kb),micrornas,pro-inflammatory genes,neurodegenerative,inflammatory disorders,autoimmune diseases

                Comments

                Comment on this article