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A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors
Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456347/ https://www.ncbi.nlm.nih.gov/pubmed/36077415 http://dx.doi.org/10.3390/ijms231710014 |
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author | Fontana, Anna Cursaro, Ilaria Carullo, Gabriele Gemma, Sandra Butini, Stefania Campiani, Giuseppe |
author_facet | Fontana, Anna Cursaro, Ilaria Carullo, Gabriele Gemma, Sandra Butini, Stefania Campiani, Giuseppe |
author_sort | Fontana, Anna |
collection | PubMed |
description | Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged as a promising target for different disorders, including X-linked intellectual disability, fibrotic diseases, cancer, and various neuropathological conditions. Selective HDAC8 targeting is required to limit side effects deriving from the treatment with pan-HDAC inhibitors (HDACis); thus, many endeavours have focused on the development of selective HDAC8is. In addition, polypharmacological approaches have been explored to achieve a synergistic action on multi-factorial diseases or to enhance the drug efficacy. In this frame, proteolysis-targeting chimeras (PROTACs) might be regarded as a dual-targeting approach for attaining HDAC8 proteasomal degradation. This review highlights the most relevant and recent advances relative to HDAC8 validation in various diseases, providing a snapshot of the current selective HDAC8is, with a focus on polyfunctional modulators. |
format | Online Article Text |
id | pubmed-9456347 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94563472022-09-09 A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors Fontana, Anna Cursaro, Ilaria Carullo, Gabriele Gemma, Sandra Butini, Stefania Campiani, Giuseppe Int J Mol Sci Review Histone deacetylases (HDACs) are epigenetic enzymes which participate in transcriptional repression and chromatin condensation mechanisms by removing the acetyl moiety from acetylated ε-amino group of histone lysines and other non-histone proteins. In recent years, HDAC8, a class I HDAC, has emerged as a promising target for different disorders, including X-linked intellectual disability, fibrotic diseases, cancer, and various neuropathological conditions. Selective HDAC8 targeting is required to limit side effects deriving from the treatment with pan-HDAC inhibitors (HDACis); thus, many endeavours have focused on the development of selective HDAC8is. In addition, polypharmacological approaches have been explored to achieve a synergistic action on multi-factorial diseases or to enhance the drug efficacy. In this frame, proteolysis-targeting chimeras (PROTACs) might be regarded as a dual-targeting approach for attaining HDAC8 proteasomal degradation. This review highlights the most relevant and recent advances relative to HDAC8 validation in various diseases, providing a snapshot of the current selective HDAC8is, with a focus on polyfunctional modulators. MDPI 2022-09-02 /pmc/articles/PMC9456347/ /pubmed/36077415 http://dx.doi.org/10.3390/ijms231710014 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Fontana, Anna Cursaro, Ilaria Carullo, Gabriele Gemma, Sandra Butini, Stefania Campiani, Giuseppe A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors |
title | A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors |
title_full | A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors |
title_fullStr | A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors |
title_full_unstemmed | A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors |
title_short | A Therapeutic Perspective of HDAC8 in Different Diseases: An Overview of Selective Inhibitors |
title_sort | therapeutic perspective of hdac8 in different diseases: an overview of selective inhibitors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9456347/ https://www.ncbi.nlm.nih.gov/pubmed/36077415 http://dx.doi.org/10.3390/ijms231710014 |
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