ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Pharmacological Selectivity Within Class I Histone Deacetylases Predicts Effects on Synaptic Function and Memory Rescue.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed, 88 citations in OpenAlex.
- Insights into neuroepigenetics through human histone deacetylase PET imaging.Science translational medicine · 2016Trial
- Discovery of a CI-994 derivative as a dual modulator of class I HDACs and Wnt/β- catenin signaling for Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2026Article
- Recommended Tool Compounds: Isoform- and Class-Specific Histone Deacetylase Inhibitors.ACS pharmacology & translational science · 2026Review
- Phytic acid (InsPNature communications · 2026Article
- CI-994 is a dual modulator of class I HDACs and Wnt/β-catenin signaling for the treatment of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Thermal shift engagement assay for Class IIA histone deacetylase inhibitor screening.Results in chemistry · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- HDAC3 as an Emerging Therapeutic Target for Alzheimer's Disease and other Neurological Disorders.Molecular neurobiology · 2025Review
- Article
- Histone Acetylation Modifications and HDACs are Associated with Resilience or Susceptibility to Stress in a Rat Model of Major Depressive Disorder.Neurochemical research · 2025Article
- Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer's disease rat model.Journal of Alzheimer's disease : JAD · 2025Article
- ZNF787 and HDAC1 Mediate Blood-Brain Barrier Permeability in an In Vitro Model of Alzheimer's Disease Microenvironment.Neurotoxicity research · 2024Article
- Class I histone deacetylases inhibition reverses memory impairment induced by acute stress in mice.PloS one · 2024Article
- Histone deacetylase 1 regulates haloperidol-induced motor side effects in aged mice.Behavioural brain research · 2023Article
- A Class I HDAC Inhibitor Rescues Synaptic Damage and Neuron Loss in APP-Transfected Cells and APP/PS1 Mice through the GRIP1/AMPA Pathway.Molecules (Basel, Switzerland) · 2022Article
- Understanding the Role of Histone Deacetylase and their Inhibitors in Neurodegenerative Disorders: Current Targets and Future Perspective.Current neuropharmacology · 2022Review
- Trichostatin A ameliorates Alzheimer's disease-related pathology and cognitive deficits by increasing albumin expression and Aβ clearance in APP/PS1 mice.Alzheimer's research & therapy · 2021Article
- Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer's Disease Model Mice.Frontiers in molecular neuroscience · 2021Article
- Histone deacetylase-3: Friend and foe of the brain.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Design, Optimization, and Study of Small Molecules That Target Tau Pre-mRNA and Affect Splicing.Journal of the American Chemical Society · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Histone deacetylases (HDACs) are promising therapeutic targets for neurological and psychiatric disorders that impact cognitive ability, but the relationship between various HDAC isoforms and cognitive improvement is poorly understood, particularly in mouse models of memory impairment. A goal shared by many is to develop HDAC inhibitors with increased isoform selectivity in order to reduce unwanted side effects, while retaining procognitive effects. However, studies addressing this tack at the molecular, cellular and behavioral level are limited. Therefore, we interrogated the biological effects of class I HDAC inhibitors with varying selectivity and assessed a subset of these compounds for their ability to regulate transcriptional activity, synaptic function and memory. The HDAC-1, -2, and -3 inhibitors, RGFP963 and RGFP968, were most effective at stimulating synaptogenesis, while the selective HDAC3 inhibitor, RGFP966, with known memory enhancing abilities, had minimal impact. Furthermore, RGFP963 increased hippocampal spine density, while HDAC3 inhibition was ineffective. Genome-wide gene expression analysis by RNA sequencing indicated that RGFP963 and RGFP966 induce largely distinct transcriptional profiles in the dorsal hippocampus of mature mice. The results of bioinformatic analyses were consistent with RGFP963 inducing a transcriptional program that enhances synaptic efficacy. Finally, RGFP963, but not RGFP966, rescued memory in a mouse model of Alzheimer's Disease. Together, these studies suggest that the specific memory promoting properties of class I HDAC inhibitors may depend on isoform selectivity and that certain pathological brain states may be more receptive to HDAC inhibitors that improve network function by enhancing synapse efficacy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.