Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1784576724129808384 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8481655 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT liulei roleofbetproteinsininflammationandcnsdiseases AT yangchangjun roleofbetproteinsininflammationandcnsdiseases AT candelariojalileduardo roleofbetproteinsininflammationandcnsdiseases |