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      The Function of NF-Kappa B During Epilepsy, a Potential Therapeutic Target

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          Abstract

          The transcriptional regulator nuclear factor kappa B (NF-κB) modulates cellular biological activity by binding to promoter regions in the nucleus and transcribing various protein-coding genes. The NF-κB pathway plays a major role in the expressing genes related to inflammation, including chemokines, interleukins, and tumor necrosis factor. It also transcribes genes that can promote neuronal survival or apoptosis. Epilepsy is one of the most common brain disorders and it not only causes death worldwide but also affects the day-to-day life of affected individuals. While epilepsy has diverse treatment options, there remain patients who are not sensitive to the existing treatment methods. Recent studies have implicated the critical role of NF-κB in epilepsy. It is upregulated in neurons, glial cells, and endothelial cells, due to neuronal loss, glial cell proliferation, blood-brain barrier dysfunction, and hippocampal sclerosis through the glutamate and γ-aminobutyric acid imbalance, ion concentration changes, and other mechanisms. In this review, we summarize the functional changes caused by the upregulation of NF-κB in the central nervous system during different periods after seizures. This review is the first to deconvolute the complicated functions of NF-κB, and speculate that the regulation of NF-κB can be a safe and effective treatment strategy for epilepsy.

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          Neurotoxic reactive astrocytes are induced by activated microglia

          A reactive astrocyte subtype termed A1 is induced after injury or disease of the central nervous system and subsequently promotes the death of neurons and oligodendrocytes.
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            ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology

            The International League Against Epilepsy (ILAE) Classification of the Epilepsies has been updated to reflect our gain in understanding of the epilepsies and their underlying mechanisms following the major scientific advances that have taken place since the last ratified classification in 1989. As a critical tool for the practicing clinician, epilepsy classification must be relevant and dynamic to changes in thinking, yet robust and translatable to all areas of the globe. Its primary purpose is for diagnosis of patients, but it is also critical for epilepsy research, development of antiepileptic therapies, and communication around the world. The new classification originates from a draft document submitted for public comments in 2013, which was revised to incorporate extensive feedback from the international epilepsy community over several rounds of consultation. It presents three levels, starting with seizure type, where it assumes that the patient is having epileptic seizures as defined by the new 2017 ILAE Seizure Classification. After diagnosis of the seizure type, the next step is diagnosis of epilepsy type, including focal epilepsy, generalized epilepsy, combined generalized, and focal epilepsy, and also an unknown epilepsy group. The third level is that of epilepsy syndrome, where a specific syndromic diagnosis can be made. The new classification incorporates etiology along each stage, emphasizing the need to consider etiology at each step of diagnosis, as it often carries significant treatment implications. Etiology is broken into six subgroups, selected because of their potential therapeutic consequences. New terminology is introduced such as developmental and epileptic encephalopathy. The term benign is replaced by the terms self-limited and pharmacoresponsive, to be used where appropriate. It is hoped that this new framework will assist in improving epilepsy care and research in the 21st century.
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              30 Years of NF-κB: A Blossoming of Relevance to Human Pathobiology.

              NF-κB was discovered 30 years ago as a rapidly inducible transcription factor. Since that time, it has been found to have a broad role in gene induction in diverse cellular responses, particularly throughout the immune system. Here, we summarize elaborate regulatory pathways involving this transcription factor and use recent discoveries in human genetic diseases to place specific proteins within their relevant medical and biological contexts.
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                Author and article information

                Contributors
                Journal
                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                1662-4548
                1662-453X
                10 March 2022
                2022
                : 16
                : 851394
                Affiliations
                Department Neurology, Bethune First Hospital of Jilin University, Jilin University , Changchun, China
                Author notes

                Edited by: Partha Sarathi Sarkar, University of Texas Medical Branch at Galveston, United States

                Reviewed by: Zucai Xu, Affiliated Hospital of Zunyi Medical University, China; Carmen Rubio, Manuel Velasco Suárez Instituto Nacional de Neurología y Neurocirugía, Mexico

                *Correspondence: Weihong Lin, linwh@ 123456jlu.edu.cn

                This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience

                Article
                10.3389/fnins.2022.851394
                8961383
                35360161
                47d74af5-adfa-44fb-ac5e-e9696870186e
                Copyright © 2022 Cai and Lin.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 09 January 2022
                : 22 February 2022
                Page count
                Figures: 1, Tables: 1, Equations: 0, References: 162, Pages: 12, Words: 10781
                Categories
                Neuroscience
                Review

                Neurosciences
                epilepsy,nf-kappa b,inflammation,chemokines,interleukins,tumor necrosis factor
                Neurosciences
                epilepsy, nf-kappa b, inflammation, chemokines, interleukins, tumor necrosis factor

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