Histone deacetylases (HDACs) and brain function

Volmar, Claude-Henry; Wahlestedt, Claes

doi:10.1016/j.nepig.2014.10.002

Cited by 151Histone Deacetylase Inhibitors ResearchEpigenetics and DNA MethylationGenomics and Chromatin Dynamics

Histone deacetylases (HDACs) and brain function

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Volmar, Claude-Henry, Wahlestedt, Claes·2015·Neuroepigenetics

DOI 10.1016/j.nepig.2014.10.002

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Abstract

Modulation of gene expression is a constant and necessary event for mammalian brain function. An important way of regulating gene expression is through the remodeling of chromatin, the complex of DNA, and histone proteins around which DNA wraps. The “histone code hypothesis” places histone post-translational modifications as a significant part of chromatin remodeling to regulate transcriptional activity. Acetylation of histones by histone acetyl transferases and deacetylation by histone deacetylases (HDACs) at lysine residues are the most studied histone post-translational modifications in cognition and neuropsychiatric diseases. Here, we review the literature regarding the role of HDACs in brain function. Among the roles of HDACs in the brain, studies show that they participate in glial lineage development, learning and memory, neuropsychiatric diseases, and even rare neurologic diseases. Most HDACs can be targeted with small molecules. However, additional brain-penetrant specific inhibitors with high central nervous system exposure are needed to determine the cause-and-effect relationship between individual HDACs and brain-associated diseases.

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Interference in nonneuronal or inappropriate neuronal locations may induce side effects and off-target effects.
“Interference in nonneuronal or inappropriate neuronal locations may induce side effects and off-target effects.409”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [409]
The Concluding remarks (page not provided) report substantial side effects in clinical trials and suggest that insufficient drug specificity or excessive dosing may explain them. The paper also says current HDAC inhibitors often affect multiple HDACs, but it does not specifically attribute side effects to interference in nonneuronal or inappropriate neuronal locations. (LLM, conf=0.84)
Experimental — accuracy not yet measured
HDACs have been implicated in a range of neuropsychiatric disorders, including depression and schizophrenia, and HDAC inhibitors could be potential cognitive enhancers in anxiety- and fear-related disorders.
“HDACs have been implicated in a range of neuropsychiatric disorders [e.g., depression and schizophrenia (358)] and HDAC inhibitors could be potential cognitive enhancers in anxiety-and fear-related disorders (359).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [358]

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Authors: Volmar, C.-H., & Wahlestedt, C.
Affiliations: University of Miami (US)
Corresponding author: Volmar, Claude-Henry
ORCID: Volmar, Claude-Henry
Wahlestedt, Claes
Venue: Neuroepigenetics
Publisher: Elsevier BV
Published: 2015-01
Volume: 1
Pages: 20-27
ISSN: 2214-7845 (ISSN-L)
DOI: 10.1016/j.nepig.2014.10.002
OpenAlex: W1970192287
Cited by: 151
References: 109
Citations by year: 2026: 7 · 2025: 8 · 2024: 6 · 2023: 14 · 2022: 11 · 2021: 13 · 2020: 18 · 2019: 12 · 2018: 23 · 2017: 19 · 2016: 15 · 2015: 5
FWCI: 5.33
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/3.0/ (vor)
Locations: Neuroepigenetics (publishedVersion, cc-by-nc-nd)
Funders: University of Miami
Pfizer’s Centers for Therapeutic Innovation
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: histone deacetylase, brain function, chromatin remodeling, histone modifications, histone acetylation, histone acetyltransferase, gene expression regulation, learning and memory, neuropsychiatric disorders, neurological disorders, histone deacetylase inhibitors, brain-penetrant drugs

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Histone deacetylases (HDACs) and brain function

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