The DOI matches its Crossref record; 83 of the 85 references it cites were found in a registry or an index.
Is there a future for histone deacetylase inhibitors in the pharmacotherapy of psychiatric disorders
Abstract
In recent years, it has become widely recognized that a comprehensive understanding of chromatin biology is necessary to better appreciate its role in a wide range of diseases. The histone code has developed as a new layer of our appreciation of transcription factor-based mechanisms of gene expression. Although epigenetic regulation refers to a host of chromatin modifications that occur at the level of DNA, histones, and histone-associated proteins, how this regulation is orchestrated is still incompletely understood. Of those processes that comprise the epigenetic regulatory machinery, DNA methylation and histone acetylation/deacetylation have been the most thoroughly studied. Compounds that act as inhibitors of DNA methyltransferases or histone deacetylases (HDACs) activate a variety of intracellular signaling pathways that ultimately affect the coordinated expression of multiple genes. The altered patterns of mRNA and protein expression collectively converge on pathways linked to apoptosis and cell cycle arrest, among others. This has prompted a widespread search for epigenetic inhibitors that could be used as chemotherapeutic agents, and several are undergoing clinical evaluation. More recently, there has been interest in the use of HDAC inhibitors to activate the expression of mRNAs that are down-regulated in various neurological and psychiatric conditions. Considerably less is known regarding the effect these drugs have on postmitotic cells such as neurons. Before we consider the clinical use of additional HDAC inhibitors to treat schizophrenia or unipolar depression, there are a number of key issues that need to be resolved.
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“An example of an epigenetic-based therapy is HDAC inhibition, which increase histone acetylation thereby relaxing the chromatic and increasing gene expression (27).”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [27]
In the citing paper
“abnormal histone modifications have been linked to multiple psychiatric disorders”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [27]
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Metadata
- Authors
- Grayson, D. R., Kundakovic, M., & Sharma, R. P.
- Affiliations
- University of Illinois Chicago (US)
- Venue
- Molecular Pharmacology
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 77
- Issue
- 2
- Pages
- 126-135
- ISSN
- 0026-895X (ISSN-L)
- OpenAlex
- W2099118364
- Cited by
- 171
- References
- 85
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 12 · 2018: 7 · 2017: 9 · 2016: 14 · 2015: 14 · 2014: 22 · 2013: 16 · 2012: 16
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Food and Drug Administration
- University of Illinois at Chicago
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Keywords
- histone deacetylase inhibitors, epigenetic regulation, chromatin biology, histone code, histone acetylation, DNA methylation, mental illness, schizophrenia, major depressive disorder, gene expression, neurons, epigenetic drugs
- MeSH terms
- Animals, Mental Disorders, Forecasting, Gene Expression Regulation, Histone Deacetylases, Humans, Histone Deacetylase Inhibitors
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