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Role of BET Proteins in Inflammation and CNS Diseases

Bromodomain and extra-terminal domain (BET) proteins consist of four mammalian members (BRD2, BRD3, BRD4, and BRDT), which play a pivotal role in the transcriptional regulation of the inflammatory response. Dysregulated inflammation is a key pathological process in various CNS disorders through mult...

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Autores principales: Liu, Lei, Yang, Changjun, Candelario-Jalil, Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481655/
https://www.ncbi.nlm.nih.gov/pubmed/34604312
http://dx.doi.org/10.3389/fmolb.2021.748449
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author Liu, Lei
Yang, Changjun
Candelario-Jalil, Eduardo
author_facet Liu, Lei
Yang, Changjun
Candelario-Jalil, Eduardo
author_sort Liu, Lei
collection PubMed
description Bromodomain and extra-terminal domain (BET) proteins consist of four mammalian members (BRD2, BRD3, BRD4, and BRDT), which play a pivotal role in the transcriptional regulation of the inflammatory response. Dysregulated inflammation is a key pathological process in various CNS disorders through multiple mechanisms, including NF-κB and Nrf2 pathways, two well-known master regulators of inflammation. A better mechanistic understanding of the BET proteins’ role in regulating the inflammatory process is of great significance since it could reveal novel therapeutic targets to reduce neuroinflammation associated with many CNS diseases. In this minireview, we first outline the structural features of BET proteins and summarize genetic and pharmacological approaches for BET inhibition, including novel strategies using proteolysis-targeting chimeras (PROTACs). We emphasize in vitro and in vivo evidence of the interplay between BET proteins and NF-κB and Nrf2 signaling pathways. Finally, we summarize recent studies showing that BET proteins are essential regulators of inflammation and neuropathology in various CNS diseases.
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spelling pubmed-84816552021-10-01 Role of BET Proteins in Inflammation and CNS Diseases Liu, Lei Yang, Changjun Candelario-Jalil, Eduardo Front Mol Biosci Molecular Biosciences Bromodomain and extra-terminal domain (BET) proteins consist of four mammalian members (BRD2, BRD3, BRD4, and BRDT), which play a pivotal role in the transcriptional regulation of the inflammatory response. Dysregulated inflammation is a key pathological process in various CNS disorders through multiple mechanisms, including NF-κB and Nrf2 pathways, two well-known master regulators of inflammation. A better mechanistic understanding of the BET proteins’ role in regulating the inflammatory process is of great significance since it could reveal novel therapeutic targets to reduce neuroinflammation associated with many CNS diseases. In this minireview, we first outline the structural features of BET proteins and summarize genetic and pharmacological approaches for BET inhibition, including novel strategies using proteolysis-targeting chimeras (PROTACs). We emphasize in vitro and in vivo evidence of the interplay between BET proteins and NF-κB and Nrf2 signaling pathways. Finally, we summarize recent studies showing that BET proteins are essential regulators of inflammation and neuropathology in various CNS diseases. Frontiers Media S.A. 2021-09-16 /pmc/articles/PMC8481655/ /pubmed/34604312 http://dx.doi.org/10.3389/fmolb.2021.748449 Text en Copyright © 2021 Liu, Yang and Candelario-Jalil. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Molecular Biosciences
Liu, Lei
Yang, Changjun
Candelario-Jalil, Eduardo
Role of BET Proteins in Inflammation and CNS Diseases
title Role of BET Proteins in Inflammation and CNS Diseases
title_full Role of BET Proteins in Inflammation and CNS Diseases
title_fullStr Role of BET Proteins in Inflammation and CNS Diseases
title_full_unstemmed Role of BET Proteins in Inflammation and CNS Diseases
title_short Role of BET Proteins in Inflammation and CNS Diseases
title_sort role of bet proteins in inflammation and cns diseases
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481655/
https://www.ncbi.nlm.nih.gov/pubmed/34604312
http://dx.doi.org/10.3389/fmolb.2021.748449
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