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Cited by 62Histone Deacetylase Inhibitors ResearchMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

Cognitive epigenetic priming: leveraging histone acetylation for memory amelioration

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Burns, Allison M, Gräff, Johannes·2021·Current Opinion in Neurobiology
DOI 10.1016/j.conb.2020.08.011
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Abstract

Multiple studies have found that increasing histone acetylation by means of histone deacetylase inhibitor (HDACi) treatment can ameliorate memory and rescue cognitive impairments, but their mode of action is not fully understood. In particular, it is unclear how HDACis, applied systemically and devoid of genomic target selectivity, would specifically improve memory-related molecular processes. One theory for such specificity is called cognitive epigenetic priming (CEP), according to which HDACis promote memory by facilitating the expression of neuroplasticity-related genes that have been stimulated by learning itself. In this review, we summarize the experimental evidence in support of CEP, describe newly discovered off-target effects of HDACis and highlight similarities between drug-induced and naturally occurring CEP. Understanding the underlying mechanisms of CEP is important in light of the preclinical premise of HDACis as cognitive enhancers.

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  • Epigenetic dysregulation through HDACs plays a critical role in synaptic dysfunction and memory loss in Alzheimer's disease.

    “Growing evidence supports that epigenetic dysregulation through histone deacetylases (HDACs) plays a critical role in synaptic dysfunction and memory loss in Alzheimer’s disease”

    From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [5]

    The sections “HDAC inhibition increases histone acetylation” and “HDAC inhibition enhances transcription” report memory impairment, altered histone acetylation, and misregulated synaptic-plasticity genes in preclinical Alzheimer’s disease models; HDAC inhibitors reversed some of these changes. The paper therefore supports a role for HDAC-related dysregulation, but the claim’s unqualified “critical role” in Alzheimer’s disease extends beyond the model-based evidence presented. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • HDAC inhibitors can enhance histone acetylation and ameliorate cognitive impairments in various AD models.

    “HDAC inhibitors can enhance histone acetylation and ameliorate cognitive impairments in various AD models, and HDAC inhibition has been recognized as an attractive therapeutic strategy for AD [4, 5, 7].”

    From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [5]

  • HDAC inhibition has been recognized as an attractive therapeutic strategy for AD.

    “HDAC inhibitors can enhance histone acetylation and ameliorate cognitive impairments in various AD models, and HDAC inhibition has been recognized as an attractive therapeutic strategy for AD [4, 5, 7].”

    From CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease (2026) · cites this paper as [5]

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Cited by

Sorted by citations

Authors
Burns, A. M., & Gräff, J.
Affiliations
École Polytechnique Fédérale de Lausanne (CH)
Corresponding author
Gräff, Johannes
ORCID
Venue
Current Opinion in Neurobiology
Publisher
Elsevier BV
Published
2021-04
Volume
67
Pages
75-84
ISSN
0959-4388 (ISSN-L)
DOI
10.1016/j.conb.2020.08.011
OpenAlex
W3097452036
Cited by
62
References
10
Citations by year
2026: 7 · 2025: 10 · 2024: 15 · 2023: 5 · 2022: 14 · 2021: 11
FWCI
0.72
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Neurobiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
  • EU Joint Programme – Neurodegenerative Disease Research
  • European Research Council
  • Vallee Foundation
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
histone acetylation, histone deacetylase inhibitors, memory enhancement, cognitive impairment, neuroplasticity, off-target effects, nootropic drugs, epigenetic memory
MeSH terms
Acetylation, Cognition, Histones, Epigenesis, Genetic, Histone Deacetylase Inhibitors

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