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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HDAC inhibition increases histone acetylation, thereby relaxing chromatin and increasing gene expression.
“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]
Abnormal histone modifications have been linked to multiple psychiatric disorders.
“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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“However, during recent years, HDACis have also received increased attention due to their putative efficacy in the therapy of psychiatric disorders (Grayson et al., 2010; Menke et al., 2012).”
BackgroundMoonat, S., Sakharkar, A. J., Zhang, H., Tang, L., & Pandey, S. C. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.01.012 · Cited by 155 · see citing works
Microbiota and Neurological Disorders: A Gut Feeling
Moos, W. H., Faller, D. V., Harpp, D. N., Kanara, I., Pernokas, J., Powers, W. R., & Steliou, K. (2016) · BioResearch open access · doi:10.1089/biores.2016.0010 · Cited by 149 · see citing works
Disease- and age-related changes in histone acetylation at gene promoters in psychiatric disorders
Tang, B., Dean, B., & Thomas, E. A. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.61 · Cited by 137 · see citing works
“role of histone acetylation on gene regulation is especially pertinent because of the therapeutic potential of HDAC inhibitors, which have gained considerable attention as a relevant therapeutic option for many neurological disorders(38,39) including psychiatric disorders.(5,40) Our previous studies have focused on no…”
BackgroundSakharkar, A. J., Zhang, H., Tang, L., Shi, G., & Pandey, S. C. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01581.x · Cited by 131 · see citing works
“Several studies indicate that epigenetic mechanisms, such as covalent histone modifications via acetylation, phosphorylation and methylation, and DNA methylation, appear to be involved in the pathophysiology of brain disorders including addictive behaviors (Feng and Fan, 2009; Grayson et al., 2010; Kazantsev and Thomp…”
BackgroundCrosstalk among Epigenetic Pathways Regulates Neurogenesis
Jobe, E. M., McQuate, A. L., & Zhao, X. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00059 · Cited by 124 · see citing works
“HDAC inhibitors are widely considered a treatment for depression (Grayson et al., 2010), and DNAmethylation inhibitors, such as 5-aza cytidine, can also lead to dose-dependent increases in BDNF expression and anti-depression effects (Sales et al.”
BackgroundFatty acids and their therapeutic potential in neurological disorders
Lei, E., Vacy, K., & Boon, W. C. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.02.014 · Cited by 123 · see citing works
Wagner, F. F., Olson, D. E., Gale, J. P., Kaya, T., Weïwer, M., Aidoud, N., Thomas, M., Davoine, E. L., Lemercier, B. C., Zhang, Y., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm301355j · Cited by 121 · see citing works
Epigenetic mechanisms in Parkinson's disease
Feng, Y., Jankovic, J. J., & Wu, Y. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.12.017 · Cited by 120 · see citing works
Jiang, Y., Jakovcevski, M., Bharadwaj, R., Connor, C., Schroeder, F. A., Lin, C. L., Straubhaar, J., Martin, G., & Akbarian, S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1314-10.2010 · Cited by 118 · see citing works
Epigenetics-beyond the genome in alcoholism.
Starkman, B. G., Sakharkar, A. J., & Pandey, S. C. (2012) · Europe PMC (PubMed Central) · Cited by 118 · see citing works
Jia, H., Morris, C. D., Williams, R. M., Loring, J. F., & Thomas, E. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415195112 · Cited by 116 · see citing works
van den Hove, D., Kenis, G., Brass, A., Opstelten, R., Rutten, B. P. F., Bruschettini, M., Blanco, C. E., Lesch, K., Steinbusch, H. W. M., & Prickaerts, J. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.09.011 · Cited by 114 · see citing works
“Interestingly, recently, several studies have highlighted the antidepressant potential of HDAC inhibitors, although numerous challenges need to be addressed before being able to guarantee sufficient specificity, potency, and a benign side effect profile of this class of drugs (Covington et al., 2011; Grayson et al., 2…”
Combination therapy: Histone deacetylase inhibitors and platinum-based chemotherapeutics for cancer
Diyabalanage, H. V. K., Granda, M. L., & Hooker, J. M. (2012) · Cancer Letters · doi:10.1016/j.canlet.2012.09.018 · Cited by 102 · see citing works
DUBs, the regulation of cell identity and disease
Heideker, J., & Wertz, I. E. (2014) · Biochemical Journal · doi:10.1042/bj20140496 · Cited by 100 · see citing works
Small Molecule Inhibitors of Zinc-dependent Histone Deacetylases
Wagner, F. F., Weïwer, M., Lewis, M. C., & Holson, E. B. (2013) · Neurotherapeutics · doi:10.1007/s13311-013-0226-1 · Cited by 99 · see citing works
“As a potential therapeutic for psychiatric diseases, HDACi have ameliorated behavioral deficits associated with schizophrenia, autism, depression, bipolar disorder, and Rubinstein–Taybi syndrome in a number of animal models [20, 23–26].”
BackgroundEpigenetics and locust life phase transitions
Ernst, U., Hiel, M. B. V., Depuydt, G., Boerjan, B., LOOF, A. D., & Schoofs, L. (2015) · Journal of Experimental Biology · doi:10.1242/jeb.107078 · Cited by 92 · see citing works
“In humans, several classes of drugs have been developed for treating cancer and psychological disorders that interact with histone modifying enzymes such as HMT, HDM, HAT or HDAC (reviewed in Grayson et al., 2010; Szyf, 2009).”
BackgroundThe potential use of histone deacetylase inhibitors in the treatment of depression
Fuchikami, M., Yamamoto, S., Morinobu, S., Okada, S., Yamawaki, Y., & Yamawaki, S. (2015) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2015.03.010 · Cited by 111 · see citing works
Epigenetics and depression: current challenges and new therapeutic options
Schroeder, M., Krebs, M., Bleich, S., & Frieling, H. (2010) · Current Opinion in Psychiatry · doi:10.1097/yco.0b013e32833d16c1 · Cited by 91 · see citing works
Sakharkar, A. J., Zhang, H., Tang, L., Baxstrom, K., Shi, G., Moonat, S., & Pandey, S. C. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145714000054 · Cited by 88 · see citing works
“HDAC-induced histone modifications have been shown to be involved in the pathophysiology of neurodegenerative and psychiatric disorders leading to the emergence of HDAC inhibitors as promising therapeutic agents (Tsankova et al., 2007; Renthal and Nestler, 2008; Grayson et al., 2010).”
BackgroundEpigenetic mechanisms in schizophrenia
Akbarian, S. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/sakbarian · Cited by 89 · see citing works
Lee, P., Murphy, B., Miller, R., Menon, V., Banik, N. L., Giglio, P., Lindhorst, S., Varma, A. K., Vandergrift, W. A., Patel, S. J., et al. (2015) · PubMed · Cited by 83 · see citing works
Effect of valproic acid on mitochondrial epigenetics
Chen, H., Dzitoyeva, S., & Manev, H. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.06.019 · Cited by 80 · see citing works
“With respect to histone acetylation, the emphasis has been on HDAC inhibitors (Chuang et al., 2009; Fischer et al., 2010; Grayson et al., 2010; Haggarty and Tsai, 2011, Kazantsev et al., 2008; Sakharkar et al., 2012).”
MethodVečeřa, J., Bártová, E., Krejčí, J., Legartová, S., Komůrková, D., Kučerová, J., Štark, T., Dražanová, E., Kašpárek, T., Šulcová, A., et al. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25914 · Cited by 80 · see citing works
“In neuropsychiatric diseases, the acetylation of histones by HATs and the functions of HDACs are the most frequently explored epigenetic features (Dean, Thomas, Lai, Chen, & Scarr, 2015; Grayson, Kundakovic, & Sharma, 2010).”
BackgroundEpigenetics, Depression and Antidepressant Treatment
Menke, A., Klengel, T., & Binder, E. B. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803523590 · Cited by 78 · see citing works
Massara, L. D., Osuru, H. P., Oklopcic, A., Milanović, D., Joksimovic, S. M., Caputo, V., DiGruccio, M. R., Ori, C., Wang, G., Todorovic, S. M., et al. (2016) · Anesthesiology · doi:10.1097/aln.0000000000001111 · Cited by 78 · see citing works
Epigenetic mechanisms of neurodegenerative diseases and acute brain injury
Bertogliat, M. J., Morris-Blanco, K. C., & Vemuganti, R. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104642 · Cited by 77 · see citing works
Epigenetic regulation of persistent pain
Bai, G., Ren, K., & Dubner, R. A. (2014) · Translational research · doi:10.1016/j.trsl.2014.05.012 · Cited by 73 · see citing works
“Considering the target specificity of sodium butyrate [172], class I and II HDACs may be involved in CCI-induced neuropathic pain.”
BackgroundValproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties
Ximenes, J. C. M., Gonçalves, D. D. O., Siqueira, R. M. P., Neves, K. R. T., Cerqueira, G. S., Correia, A. O., Felix, F. H. C., Leal, L. K. A. M., Brito, G. A. D. C., Naffah‐Mazzacoratti, M. D. G., et al. (2013) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-013-0853-4 · Cited by 72 · see citing works
“Evidences show that although VA and SAHA bind to the catalytic site of the HDAC molecule (Göttlicher et al. 2001; Krämer et al. 2003; Villar-Garea and Esteller 2004; Lin et al. 2006), VA is less potent in inhibiting HDAC activity than SAHA (Grayson et al. 2010).”
Ma, K., Qin, L., Matas, E., Duffney, L. J., Liu, A., & Yan, Z. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0073-1 · Cited by 71 · see citing works
Albert, P. R., François, B. L., & Vahid-Ansari, F. (2019) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.180209 · Cited by 71 · see citing works
Histone deacetylases (HDACs) as therapeutic target for depressive disorders
Misztak, P., Pańczyszyn-Trzewik, P., & Sowa-Kućma, M. (2017) · Pharmacological Reports · doi:10.1016/j.pharep.2017.08.001 · Cited by 70 · see citing works
Zhang, S., Fujita, Y., Matsuzaki, R., & Yamashita, T. (2018) · Cell Death & Disease · doi:10.1038/s41419-018-0543-8 · Cited by 68 · see citing works
Soria-Castro, R., Schcolnik‐Cabrera, A., Rodríguez-López, G. M., Campillo-Navarro, M., Puebla‐Osorio, N., Estrada-Parra, S. A., Estrada‐García, I., Chacón‐Salinas, R., & Chávez-Blanco, A. D. (2019) · Journal of Immunology Research · doi:10.1155/2019/9678098 · Cited by 68 · see citing works
“Currently, VPA and more HDACIs are therapeutic alternatives, and most of them have been approved for clinical use [37].”
BackgroundLysine Acetylation and Deacetylation in Brain Development and Neuropathies
Tapias, A., & Wang, Z. (2017) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2016.09.002 · Cited by 66 · see citing works
“HDACi has been used to treat different human diseases, including cancer [164], cardiovascular diseases [164], inflammatory diseases [165], and a range of psychiatric disorders [21,166].”
BackgroundInterindividual Variability in Stress Susceptibility: A Role for Epigenetic Mechanisms in PTSD
Zovkic, I. B., Meadows, J. P., Kaas, G. A., & Sweatt, J. D. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00060 · Cited by 62 · see citing works
“Similarly, positive outcomes were reported for the HDACi valproic acid when given in conjunction with antipsychotics (Wassef et al., 2000, 2001; Grayson et al., 2010) or anti-depressants (Schroeder et al., 2007).”
BackgroundEpigenetics: a link between addiction and social environment
Ajonijebu, D. C., Abboussi, O., Russell, V. A., Mabandla, M. V., & Daniels, W. M. U. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2493-1 · Cited by 65 · see citing works
“Increased or low levels of histone acetylation within specific promoter regions correlates with enhanced or repressed gene activity, respectively [31].”
BackgroundInfluentialNew Therapeutic Targets for Mood Disorders
Machado‐Vieira, R., Salvadore, G., Diazgranados, N., Ibrahim, L. A., Latov, D. R., Wheeler‐Castillo, C., Baumann, J., Henter, I. D., & Zarate, C. A. (2010) · The Scientific World JOURNAL · doi:10.1100/tsw.2010.65 · Cited by 61 · see citing works
“In neuronal tissue, HDAC inhibitors limit histone deacetylation mostly by inactivating class I or II HDACs, thus increasing histone acetylation (for a review see Grayson et al.[55]).”
Pharmacotherapy for anxiety disorders in children and adolescents
Kodish, I., Rockhill, C., & Varley, C. (2011) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2011.13.4/ikodish · Cited by 62 · see citing works
Ethanol actions on the ventral tegmental area: novel potential targets on reward pathway neurons
You, C., Vandegrift, B. J., & Brodie, M. S. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4875-y · Cited by 62 · see citing works
“Fortunately, there are a number of drugs that target epigenetic enzymes; although originally developed for the treatment of specific cancers, application of these agents to psychiatric disorders, including alcohol and substance use disorders, may be possible (Grayson et al. 2010).”
BackgroundUnveiling the role of histone deacetylases in neurological diseases: focus on epilepsy
Cao, D., Zhou, X., Guo, Q., Xiang, M.-Y., Bao, M., He, B., & Mao, X. (2024) · Biomarker Research · doi:10.1186/s40364-024-00687-6 · Cited by 59 · see citing works
“To the best of our knowledge, there are hitherto at least four categories of HDACi, namely, SCFAs, hydroxamates, cyclic peptides and benzamides according to their distinctive chemical structures [127], as summarized in Fig.”
Role of Histone Deacetylases (HDACs) in Epilepsy and Epileptogenesis
Citraro, R., Leo, A., Santoro, M., D’Agostino, G., Constanti, A., & Russo, E. (2018) · Current Pharmaceutical Design · doi:10.2174/1381612823666171024130001 · Cited by 58 · see citing works
“SCFAs all show the same inhibition profile on the HDAC I and IIa classes with most efficacy in inhibiting the HDAC activity than hydroxamates [81].”
InfluentialEpigenetic Treatment of Neurodegenerative Disorders: Alzheimer and Parkinson Diseases
Irwin, M. H., Moos, W. H., Faller, D. V., Steliou, K., & Pinkert, C. A. (2016) · Drug Development Research · doi:10.1002/ddr.21294 · Cited by 56 · see citing works
“, 2013; Natarajan and Pluznick, 2014], and its potential use in the intervention of neurodegenerative diseases and psychiatric disorders is of longstanding interest [Chuang et al., 2009; Thomas, 2009; Grayson et al., 2010; Canani et al., 2012; Harrison and Dexter, 2013; Rosenstock, 2013; De Vadder et al., 2014; Sezgin…”
BackgroundThomas, E. A. (2014) · Pharmaceuticals · doi:10.3390/ph7060634 · Cited by 51 · see citing works
“A large majority of hydroxamate HDAC inhibitors act as pan-HDAC inhibitors, and do not show selectivity within the zinc dependent classes of HDAC enzymes [53]; however due to the large variation in chemical structure among peptides, peptide HDAC inhibitors can elicit inhibition of different HDAC isoforms, including mo…”
BackgroundTranscriptional dysregulation in Huntington’s disease: The role of histone deacetylases
Sharma, S., & Taliyan, R. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.08.002 · Cited by 53 · see citing works
Repurposing Vorinostat for the Treatment of Disorders Affecting Brain
Athira, K. V., Sadanandan, P., & Chakravarty, S. (2021) · NeuroMolecular Medicine · doi:10.1007/s12017-021-08660-4 · Cited by 52 · see citing works
“A number of HDAC inhibitors have been developed belonging to various classes (Table 1) (Didonna & Opal, 2015; Grayson et al., 2010; Souza, 2015; Wash et al., 2008).”
BackgroundHistone deacetylase inhibitors as potential treatment for spinal muscular atrophy
Mohseni, J. H., Zabidi-Hussin, Z. A. M. H., & Sasongko, T. H. (2013) · Genetics and Molecular Biology · doi:10.1590/s1415-47572013000300001 · Cited by 52 · see citing works
“In this regard, HDACs are actually “lysinedeacetylases” (Grayson et al., 2010; Xu et al., 2007).”
BackgroundHasan, A., Mitchell, A., Schneider, A., Halene, T. B., & Akbarian, S. (2013) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-013-0395-2 · Cited by 51 · see citing works
“monotherapy versus combination therapy (especially with antipsychotics), and most importantly (4) safety and a benign side effect profile [46].”
BackgroundInfluentialVargas-Martínez, F., Uvnás-Moberg, K., Petersson, M., Olausson, H., & Jiménez-Estrada, I. (2014) · Progress in neurobiology · doi:10.1016/j.pneurobio.2014.10.001 · Cited by 49 · see citing works
Epigenomic mediation after adverse childhood experiences: a systematic review and meta-analysis
Neves, I., Dinis‐Oliveira, R. J., & Magalhães, T. (2019) · Forensic Sciences Research · doi:10.1080/20961790.2019.1641954 · Cited by 51 · see citing works
Pirooznia, S. K., & Elefant, F. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00030 · Cited by 51 · see citing works
“Accordingly, local administration of HDACi in such brain regions has been observed to have antidepressant-like actions in several behavioral assays (Schroeder et al., 2007; Bredy and Barad, 2008; Grayson et al., 2010).”
BackgroundThe epigenetic regulation of HIF-1α by SIRT1 in MPP + treated SH-SY5Y cells
Dong, S., Guo, Y., Feng, Y., Cui, X., Kuo, S., Liu, T., & Wu, Y. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.01.013 · Cited by 49 · see citing works
“Histone acetylation plays a significant role in regulating gene transcription [15,16].”
BackgroundExperience and the ever‐changing brain: What the transcriptome can reveal
Rubin, T. G., Gray, J. D., & McEwen, B. S. (2014) · BioEssays · doi:10.1002/bies.201400095 · Cited by 47 · see citing works
“Importantly, the use of drugs that can manipulate the levels of these modifying enzymes are already being explored for the treatment of mental illnesses [18].”
BackgroundAntistress properties of antidepressant drugs and their clinical implications
Calabrese, F., Molteni, R., & Riva, M. A. (2011) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2011.05.007 · Cited by 41 · see citing works
Stertz, L., Fries, G. R., de Aguiar, B. W., Pfaffenseller, B., Valvassori, S. S., Gubert, C., Ferreira, C. L., Moretti, M., Ceresér, K. M. M., Kauer‐Sant’Anna, M., et al. (2013) · Brazilian Journal of Psychiatry · doi:10.1590/1516-4446-2013-1094 · Cited by 40 · see citing works
Renani, P. G., Taheri, F., Rostami, D., Farahani, N., Abdolkarimi, H., Abdollahi, E., Taghizadeh, E., & Hayat, S. M. G. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28622 · Cited by 40 · see citing works
Qin, L., Ma, K., & Yan, Z. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-021-01212-1 · Cited by 41 · see citing works
“Increased HDAC expression and ensuring transcriptional dysfunction involved in synaptic transmission have been implicated in psychiatric disorders [5, 6].”
BackgroundEpigenetic Treatment of Neuropsychiatric Disorders: Autism and Schizophrenia
Moos, W. H., Maneta, E., Pinkert, C. A., Irwin, M. H., Hoffman, M. E., Faller, D. V., & Steliou, K. (2016) · Drug Development Research · doi:10.1002/ddr.21295 · Cited by 40 · see citing works
“With respect to epigenetic mechanisms, including HDACs and their inhibition, SCFAs like butyrate have a profound influence on microglial homeostasis [Erny et al., 2015].”
BackgroundInfluentialThe possibility of evidence-based psychiatry: depression as a case
Stojanov, D., Korf, J., de Jonge, P., & Popov, G. (2010) · Clinical Epigenetics · doi:10.1007/s13148-010-0014-2 · Cited by 35 · see citing works
“Most recently, there are experimental data reported (Grayson et al. 2010) which suggest the application of inhibitors of DNA methyl transferase and histone deacetylase (HDAC) as potential therapeutic agents in the causal treatments of psychiatric disorders.”
BackgroundClass I HDAC Inhibitors: Potential New Epigenetic Therapeutics for Alcohol Use Disorder (AUD)
Bourguet, E., Ozdarska, K., Moroy, G., Jeanblanc, J., & Naassila, M. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00115 · Cited by 36 · see citing works
Chakravarty, S., Maitra, S., Reddy, R. G., Das, T., Jhelum, P., Kootar, S., Rajan, W. D., Samanta, A., Samineni, R., Pabbaraja, S., et al. (2015) · Scientific Reports · doi:10.1038/srep14134 · Cited by 32 · see citing works
Bi, M., Feng, L., He, J., Liu, C., Wang, Y., Jiang, H., & Liu, S. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101759 · Cited by 32 · see citing works
The Epigenetic Code in Depression: Implications for Treatment
Schroeder, M., Hillemacher, T., Bleich, S., & Frieling, H. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.282 · Cited by 32 · see citing works
Class I HDAC imaging using [3H]CI-994 autoradiography
Wang, Y., Zhang, Y., Hennig, K. M., Gale, J. P., Hong, Y., Cha, A., Riley, M. M., Wagner, F. F., Haggarty, S. J., Holson, E. B., et al. (2013) · Epigenetics · doi:10.4161/epi.25202 · Cited by 30 · see citing works
Balasubramanian, D., Deng, A. X., Doudney, K., Hampton, M. B., & Kennedy, M. A. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.06.018 · Cited by 29 · see citing works
Zhang, F., Rein, B. A., Zhong, P., Shwani, T., Conrow‐Graham, M., Wang, Z., & Yan, Z. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01233-w · Cited by 29 · see citing works
Epigenetic Regulatory Mechanisms in Stress-Induced Behavior
Chakravarty, S., Pathak, S. S., Maitra, S., Khandelwal, N., Karisetty, B. C., & Kumar, A. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-801311-3.00004-4 · Cited by 29 · see citing works
Plazas-Mayorca, M. D., & Vrana, K. E. (2010) · Journal of Proteome Research · doi:10.1021/pr100463y · Cited by 27 · see citing works
Inflammation as a Mechanism of Bipolar Disorder Neuroprogression
Barichello, T., Giridharan, V. V., Bhatti, G. S., Sayana, P., Doifode, T., Macêdo, D. S., & Quevedo, J. (2020) · Current topics in behavioral neurosciences · doi:10.1007/7854_2020_173 · Cited by 27 · see citing works
Pharmacogenomic Implications of Variants of Monoaminergic-Related Genes in Geriatric Psychiatry
Shiroma, P. R., Geda, Y. E., & Mrazek, D. A. (2010) · Pharmacogenomics · doi:10.2217/pgs.10.118 · Cited by 26 · see citing works
Is there any therapeutic value for the use of histone deacetylase inhibitors for chronic pain?
Wang, W., Cui, S.-S., Lu, R., & Zhang, H. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.04.010 · Cited by 26 · see citing works
Epigenetic approaches for bipolar disorder drug discovery
Peedicayil, J. (2014) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2014.922537 · Cited by 25 · see citing works
“It appears that those HDACis that facilitate DNA demethylation have greater efficacy than those that do not [19,20].”
BackgroundLi, Y.-C., Panikker, P., Xing, B., Yang, S.-S., Alexandropoulos, C., McEachern, E., Akumuo, R. C., Zhao, E. E., Gulchina, Y., Pletnikov, M. V., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.10.025 · Cited by 24 · see citing works
Epigenetic management of major psychosis
Peedicayil, J. (2011) · Clinical Epigenetics · doi:10.1007/s13148-011-0038-2 · Cited by 24 · see citing works
“Epigenetic drugs that are being investigated for such a purpose include SAHA (vorinostat), MS275, and phenylbutyrate (Best and Carey 2010; Grayson et al. 2010).”
BackgroundSchizophrenia and the Epigenetic Hypothesis
Grayson, D. R. (2010) · Epigenomics · doi:10.2217/epi.10.22 · Cited by 22 · see citing works
Histone deacetylases and inhibitors in diabetes mellitus and its complications
Wang, L., Bai, Y., Cao, Z., Guo, Z., Lian, Y., Liu, P., Zeng, Y., Lyu, W., & Chen, Q. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117010 · Cited by 24 · see citing works
Histone Deacetylase Inhibitors as Cognitive Enhancers and Modifiers of Mood and Behavior
Pal, D., Sahu, P., Mishra, A. K., Hagelgans, A., & Sukocheva, O. A. (2022) · Current Drug Targets · doi:10.2174/1389450124666221207090108 · Cited by 19 · see citing works
Comparison of Different Histone Deacetylase Inhibitors in Attenuating Inflammatory Pain in Rats
Mao, Y., Zhou, J., Liu, X., Gu, E., Zhang, Z., & Tao, W. (2019) · Pain Research and Management · doi:10.1155/2019/1648919 · Cited by 20 · see citing works
“Although Table 1 lists the sensitivities of tested drugs to the isoforms of HDAC classes [63, 65], our results provided di erent HDACI e¢cacies in rat models of persistent inammatory pain.”
ResultZhou, Q., Dalgard, C. L., Wynder, C., & Doughty, M. L. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.06.037 · Cited by 19 · see citing works
“Furthermore, at high doses VPA inhibits histone deacetylase (HDAC) activity [11] and HDACmediated responses are proposed to contribute to the differential neurogenic effects of VPA in the normal and epileptic adult rodent brain [14,15,23].”
Auta, J., Gatta, E., Davis, J. M., Pandey, S. C., & Guidotti, A. (2018) · Pharmacology Research & Perspectives · doi:10.1002/prp2.416 · Cited by 19 · see citing works
“17 Conversely, DNA promoter methylation which involves the covalent coupling of a methyl group to the C5 position of cytosine residues of CpG dinucleotide upstream of the transcription start site, is catalyzed by DNA methyltransferases [DNA methyltransferase 1 (Dnmt1), DNA methyltransferase 3a (Dnmt13a) DNA methyltran…”
BackgroundGenome-Wide Screening for Genes Associated with Valproic Acid Sensitivity in Fission Yeast
Zhang, L., Ma, N., Liu, Q., & Ma, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068738 · Cited by 18 · see citing works
“HDAC inhibitors could benefit diseases such as neurological and psychiatric disorders [11].”
BackgroundGavin, D. P., & Floreani, C. V. (2014) · International review of neurobiology · doi:10.1016/b978-0-12-801311-3.00005-6 · Cited by 17 · see citing works
Histone deacetylase inhibition is cytotoxic to oligodendrocyte precursor cells in vitro and in vivo
Dincman, T. A., Beare, J. E., Ohri, S. S., Gallo, V., Hetman, M., & Whittemore, S. R. (2016) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2016.08.006 · Cited by 18 · see citing works
Lopez, Y. P., Kenis, G., Stettinger, W., Neumeier, K., de Jonge, S., Steinbusch, H. W. M., Zill, P., van den Hove, D., & Myint, A.-M. (2016) · Molecular Biology Reports · doi:10.1007/s11033-016-4006-y · Cited by 17 · see citing works
“Vice versa, HDAC inhibitors have also been shown to possess antidepressant properties [32, 33].”
Mechanism of methylation and acetylation of high GDNF transcription in glioma cells: A review
Zhang, L., Wang, D., Han, X., Tang, F., & Gao, D. (2019) · Heliyon · doi:10.1016/j.heliyon.2019.e01951 · Cited by 17 · see citing works
Preventing epigenetic traces of caregiver maltreatment: A role for HDAC inhibition
Doherty, T. S., Chajes, J. R., Reich, L., Duffy, H. B. D., & Roth, T. (2019) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2019.05.002 · Cited by 11 · see citing works
“drugs were first used in cancer therapy, they may be effective in treating various psychopathologies (Grayson et al., 2010; Shepard et al., 2018; Szyf, 2009; Varela et al., 2015) and physical health problems following early adversity (Moloney et al.”
BackgroundMethod
- 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 › 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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