The acetylation of histone and non-histone proteins controls a great deal of cellular functions, thereby affecting the entire organism, including the brain. Acetylation modifications are mediated through histone acetyltransferases (HAT) and deacetylases (HDAC), and the balance of these enzymes regulates neuronal homeostasis, maintaining the pre-existing acetyl marks responsible for the global chromatin structure, as well as regulating specific dynamic acetyl marks that respond to changes and facilitate neurons to encode and strengthen long-term events in the brain circuitry (e.g., memory formation). Unfortunately, the dysfunction of these finely-tuned regulations might lead to pathological conditions, and the deregulation of the HAT/HDAC balance has been implicated in neurological disorders. During the last decade, research has focused on HDAC inhibitors that induce a histone hyperacetylated state to compensate acetylation deficits. The use of these inhibitors as a therapeutic option was efficient in several animal models of neurological disorders. The elaboration of new cell-permeant HAT activators opens a new era of research on acetylation regulation. Although pathological animal models have not been tested yet, HAT activator molecules have already proven to be beneficial in ameliorating brain functions associated with learning and memory, and adult neurogenesis in wild-type animals. Thus, HAT activator molecules contribute to an exciting area of research.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Izzo A, Schneider R. Chatting histone modifications in mammals. Brief Funct Genomics 2010;9:429–443.
Lee JS, Smith E, Shilatifard A. The language of histone crosstalk. Cell 2010;142:682–685.
Allis CD, Berger SL, Cote J, et al. New nomenclature for chromatin-modifying enzymes. Cell 2007;131:633–636.
McBrian MA, Behbahan IS, Ferrari R, et al. Histone acetylation regulates intracellular pH. Mol Cell 2013;49:310–321.
Abel T, Zukin RS. Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders. Curr Opin Pharmacol 2008;8:57–64.
Chuang DM, Leng Y, Marinova Z, Kim HJ, Chiu CT. Multiple roles of HDAC inhibition in neurodegenerative conditions. Trends Neurosci 2009;32:591–601.
Selvi BR, Cassel JC, Kundu TK, Boutillier AL. Tuning acetylation levels with HAT activators: therapeutic strategy in neurodegenerative diseases. Biochim Biophys Acta 2010;1799:840–853.
Steffan JS, Bodai L, Pallos J, et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001;413:739–743.
Steffan JS, Kazantsev A, Spasic-Boskovic O, et al. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc Natl Acad Sci U S A 2000;97:6763–6768.
Minamiyama M, Katsuno M, Adachi H, et al. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum Mol Genet 2004;13:1183–1192.
Graff J, Kim D, Dobbin MM, Tsai LH. Epigenetic regulation of gene expression in physiological and pathological brain processes. Physiol Rev 2011;91:603–649.
Sleiman SF, Basso M, Mahishi L, et al. Putting the 'HAT' back on survival signalling: the promises and challenges of HDAC inhibition in the treatment of neurological conditions. Expert Opin Investig Drugs 2009;18:573–584.
Dash PK, Orsi SA, Moore AN. Histone deactylase inhibition combined with behavioral therapy enhances learning and memory following traumatic brain injury. Neuroscience 2009;163:1–8.
Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai LH. Recovery of learning and memory is associated with chromatin remodelling. Nature 2007;447:178–182.
Peleg S, Sananbenesi F, Zovoilis A, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 2010;328:753–756.
Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 2007;25:84–90.
Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 2009;325:834–840.
Zhao S, Xu W, Jiang W, et al. Regulation of cellular metabolism by protein lysine acetylation. Science 2010;327:1000–1004.
Lundby A, Lage K, Weinert BT, et al. Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns. Cell Rep 2012;2:419–431.
Zeng L, Zhou MM. Bromodomain: an acetyl-lysine binding domain. FEBS Lett 2002;513:124–128.
You L, Nie J, Sun WJ, Zheng ZQ, Yang XJ. Lysine acetylation: enzymes, bromodomains and links to different diseases. Essays Biochem 2012;52:1–12.
Livengood JA, Scoggin KE, Van Orden K, et al. p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300. J Biol Chem 2002;277:9054–9061.
Sanjuan R, Marin I. Tracing the origin of the compensasome: evolutionary history of DEAH helicase and MYST acetyltransferase gene families. Mol Biol Evol 2001;18:330–343.
Sterner DE, Berger SL. Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev 2000;64:435–459.
Lassar AB, Martin PL, Roeder RG. Transcription of class III genes: formation of preinitiation complexes. Science 1983;222:740–748.
Kundu TK, Wang Z, Roeder RG. Human TFIIIC relieves chromatin-mediated repression of RNA polymerase III transcription and contains an intrinsic histone acetyltransferase activity. Mol Cell Biol 1999;19:1605–1615.
Sadoul K, Wang J, Diagouraga B, Khochbin S. The tale of protein lysine acetylation in the cytoplasm. J Biomed Biotechnol 2011;2011:970382.
Kornberg RD, Lorch Y. Chromatin-modifying and -remodeling complexes. Curr Opin Genet Develop 1999;9:148–151.
Struhl K. Histone acetylation and transcriptional regulatory mechanisms. Genes Develop 1998;12:599–606.
Clarke AS, Lowell JE, Jacobson SJ, Pillus L. Esa1p is an essential histone acetyltransferase required for cell cycle progression. Mol Cell Biol 1999;19:2515–2526.
Iizuka M, Stillman B. Histone acetyltransferase HBO1 interacts with the ORC1 subunit of the human initiator protein. J Biol Chem 1999;274:23027–23034.
Magnaghi-Jaulin L, Ait-Si-Ali S, Harel-Bellan A. Histone acetylation and the control of the cell cycle. Prog Cell Cycle Res 2000;4:41–47.
Smith ER, Eisen A, Gu W, et al. ESA1 is a histone acetyltransferase that is essential for growth in yeast. Proc Natl Acad Sci U S A 1998;95:3561–3565.
Chatterjee S, Senapati P, Kundu TK. Post-translational modifications of lysine in DNA-damage repair. Essays Biochem 2012;52:93–111.
Blanco JC, Minucci S, Lu J, et al. The histone acetylase PCAF is a nuclear receptor coactivator. Genes Develop 1998;12:1638–1651.
Thompson PR, Wang D, Wang L, et al. Regulation of the p300 HAT domain via a novel activation loop. Nat Struct Mol Biol 2004;11:308–315.
Black JC, Mosley A, Kitada T, Washburn M, Carey M. The SIRT2 deacetylase regulates autoacetylation of p300. Mol Cell 2008;32:449–455.
Gregoire S, Xiao L, Nie J, et al. Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2. Mol Cell Biol 2007;27:1280–1295.
Wang J, Chen J. SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60. J Biol Chem 2010;285:11458–11464.
Bengtson CP, Bading H. Nuclear calcium signaling. Adv Exp Med Biol 2012;970:377–405.
Vo N, Goodman RH. CREB-binding protein and p300 in transcriptional regulation. J Biol Chem 2001;276:13505–13508.
Chevillard-Briet M, Trouche D, Vandel L. Control of CBP co-activating activity by arginine methylation. EMBO J 2002;21:5457–5466.
Daujat S, Bauer UM, Shah V, Turner B, Berger S, Kouzarides T. Crosstalk between CARM1 methylation and CBP acetylation on histone H3. Curr Biol 2002;12:2090–2097.
Soliman ML, Rosenberger TA. Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression. Mol Cell Biochem 2011;352:173–180.
Kalkhoven E, Roelfsema JH, Teunissen H, et al. Loss of CBP acetyltransferase activity by PHD finger mutations in Rubinstein-Taybi syndrome. Hum Mol Genet 2003;12:441–450.
Kung AL, Rebel VI, Bronson RT, et al. Gene dose-dependent control of hematopoiesis and hematologic tumor suppression by CBP. Genes Develop 2000;14:272–277.
Oike Y, Hata A, Mamiya T, et al. Truncated CBP protein leads to classical Rubinstein-Taybi syndrome phenotypes in mice: implications for a dominant-negative mechanism. Hum Mol Genet 1999;8:387–396.
Shikama N, Lutz W, Kretzschmar R, et al. Essential function of p300 acetyltransferase activity in heart, lung and small intestine formation. EMBO J 2003;22:5175–5185.
Yao TP, Oh SP, Fuchs M, et al. Gene dosage-dependent embryonic development and proliferation defects in mice lacking the transcriptional integrator p300. Cell 1998;93:361–372.
Tanaka Y, Naruse I, Hongo T, et al. Extensive brain hemorrhage and embryonic lethality in a mouse null mutant of CREB-binding protein. Mech Develop 2000;95:133–145.
Nakashima K, Yanagisawa M, Arakawa H, et al. Synergistic signaling in fetal brain by STAT3-Smad1 complex bridged by p300. Science 1999;284:479–482.
Lee S, Lee B, Lee JW, Lee SK. Retinoid signaling and neurogenin2 function are coupled for the specification of spinal motor neurons through a chromatin modifier CBP. Neuron 2009;62:641–654.
Sun Y, Nadal-Vicens M, Misono S, et al. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms. Cell 2001;104:365–376.
Wang J, Weaver IC, Gauthier-Fisher A, et al. CBP histone acetyltransferase activity regulates embryonic neural differentiation in the normal and Rubinstein-Taybi syndrome brain. Develop Cell 2010;18:114–125.
Bu P, Evrard YA, Lozano G, Dent SY. Loss of Gcn5 acetyltransferase activity leads to neural tube closure defects and exencephaly in mouse embryos. Mol Cell Biol 2007;27:3405–3416.
Lin W, Zhang Z, Srajer G, et al. Proper expression of the Gcn5 histone acetyltransferase is required for neural tube closure in mouse embryos. Dev Dyn 2008;237:928–940.
Xu W, Edmondson DG, Evrard YA, Wakamiya M, Behringer RR, Roth SY. Loss of Gcn5l2 leads to increased apoptosis and mesodermal defects during mouse development. Nat Genetics 2000;26:229–232.
Yamauchi T, Yamauchi J, Kuwata T, et al. Distinct but overlapping roles of histone acetylase PCAF and of the closely related PCAF-B/GCN5 in mouse embryogenesis. Proc Natl Acad Sci U S A 2000;97:11303–11306.
Chen YC, Gatchel JR, Lewis RW, et al. Gcn5 loss-of-function accelerates cerebellar and retinal degeneration in a SCA7 mouse model. Hum Mol Genetics 2012;21:394–405.
Martinez-Cerdeno V, Lemen JM, Chan V, et al. N-Myc and GCN5 regulate significantly overlapping transcriptional programs in neural stem cells. PloS One 2012;7:e39456.
Gehrking KM, Andresen JM, Duvick L, Lough J, Zoghbi HY, Orr HT. Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genetics 2011;20:2204–2212.
Ye F, Chen Y, Hoang T, et al. HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci 2009;12:829–838.
Lyssiotis CA, Walker J, Wu C, Kondo T, Schultz PG, Wu X. Inhibition of histone deacetylase activity induces developmental plasticity in oligodendrocyte precursor cells. Proc Natl Acad Sci U S A 2007;104:14982–14987.
Marin-Husstege M, Muggironi M, Liu A, Casaccia-Bonnefil P. Histone deacetylase activity is necessary for oligodendrocyte lineage progression. J Neurosci 2002;22:10333–10345.
Lau OD, Kundu TK, Soccio RE, et al. HATs off: selective synthetic inhibitors of the histone acetyltransferases p300 and PCAF. Mol Cell 2000;5:589–595.
Collins HM, Abdelghany MK, Messmer M, et al. Differential effects of garcinol and curcumin on histone and p53 modifications in tumour cells. BMC Cancer 2013;13:37.
Selvi BR, Chatterjee S, Modak R, Eswaramoorthy M, Kundu TK. Histone acetylation as a therapeutic target. Subcell Biochem 2012;61:567–596.
Swaminathan V, Reddy BA, Ruthrotha Selvi B, Sukanya MS, Kundu TK. Small molecule modulators in epigenetics: implications in gene expression and therapeutics. Subcell Biochem 2007;41:397–428.
Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK. Small molecule modulators of histone acetyltransferase p300. J Biol Chem 2003;278:19134–19140.
Souto JA, Benedetti R, Otto K, et al. New anacardic acid-inspired benzamides: histone lysine acetyltransferase activators. ChemMedChem 2010;5:1530–1540.
Mantelingu K, Kishore AH, Balasubramanyam K, et al. Activation of p300 histone acetyltransferase by small molecules altering enzyme structure: probed by surface-enhanced Raman spectroscopy. J Phys Chem B 2007;111:4527–4534.
Chatterjee S, Mizar P, Cassel R, et al. A novel activator of CBP/p300 acetyltransferases promotes neurogenesis and extends memory duration in adult mice. J Neurosci 2013;33:10698–10712.
Dal Piaz F, Tosco A, Eletto D, et al. The identification of a novel natural activator of p300 histone acetyltranferase provides new insights into the modulation mechanism of this enzyme. Chembiochem 2010;11:818–827.
Milite C, Castellano S, Benedetti R, et al. Modulation of the activity of histone acetyltransferases by long chain alkylidenemalonates (LoCAMs). Bioorg Med Chem 2011;19:3690–3701.
Sbardella G, Castellano S, Vicidomini C, et al. Identification of long chain alkylidenemalonates as novel small molecule modulators of histone acetyltransferases. Bioorg Med Chem Lett 2008;18:2788–2792.
Rouaux C, Jokic N, Mbebi C, Boutillier S, Loeffler JP, Boutillier AL. Critical loss of CBP/p300 histone acetylase activity by caspase-6 during neurodegeneration. EMBO J 2003;22:6537–6549.
Rouaux C, Loeffler JP, Boutillier AL. Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders. Biochem Pharmacol 2004;68:1157–1164.
Saha RN, Pahan K. HATs and HDACs in neurodegeneration: a tale of disconcerted acetylation homeostasis. Cell Death Differ 2006;13:539–550.
Kumar P, Kalonia H, Kumar A. Huntington's disease: pathogenesis to animal models. Pharmacol Rep 2010;62:1–14.
Orr HT, Zoghbi HY. Trinucleotide repeat disorders. Annu Rev Neurosci 2007;30:575–621.
Kazantsev A, Preisinger E, Dranovsky A, Goldgaber D, Housman D. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc Natl Acad Sci U S A 1999;96:11404–11409.
Cong SY, Pepers BA, Evert BO, et al. Mutant huntingtin represses CBP, but not p300, by binding and protein degradation. Mol Cell Neurosci 2005;30:560–571.
Jiang H, Poirier MA, Liang Y, et al. Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin. Neurobiol Dis 2006;23:543–551.
Choi YJ, Kim SI, Lee JW, et al. Suppression of aggregate formation of mutant huntingtin potentiates CREB-binding protein sequestration and apoptotic cell death. Mol Cell Neurosci 2012;49:127–137.
Wilburn B, Rudnicki DD, Zhao J, et al. An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. Neuron 2011;70:427–440.
Bodai L, Pallos J, Thompson LM, Marsh JL. Pcaf modulates polyglutamine pathology in a Drosophila model of Huntington's disease. Neurodegener Dis 2012;9:104–106.
Choi YS, Lee B, Cho HY, et al. CREB is a key regulator of striatal vulnerability in chemical and genetic models of Huntington's disease. Neurobiol Dis 2009;36:259–268.
Giralt A, Puigdellivol M, Carreton O, et al. Long-term memory deficits in Huntington's disease are associated with reduced CBP histone acetylase activity. Hum Mol Genet 2012;21:1203–1216.
Quinti L, Chopra V, Rotili D, et al. Evaluation of histone deacetylases as drug targets in Huntington's disease models. Study of HDACs in brain tissues from R6/2 and CAG140 knock-in HD mouse models and human patients and in a neuronal HD cell model. PLoS Curr 2010;2.
Bae BI, Xu H, Igarashi S, et al. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005;47:29–41.
Jeong H, Then F, Melia TJ, Jr, et al. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 2009;137:60–72.
Lee J, Hwang YJ, Boo JH, et al. Dysregulation of upstream binding factor-1 acetylation at K352 is linked to impaired ribosomal DNA transcription in Huntington's disease. Cell Death Differ 2011;18:1726–1735.
Reed NA, Cai D, Blasius TL, et al. Microtubule acetylation promotes kinesin-1 binding and transport. Curr Biol 2006;16:2166–2172.
Nguyen T, Mehta NR, Conant K, et al. Axonal protective effects of the myelin-associated glycoprotein. J Neurosci 2009;29:630–637.
Gauthier LR, Charrin BC, Borrell-Pages M, et al. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004;118:127–138.
McFarland KN, Das S, Sun TT, et al. Genome-wide histone acetylation is altered in a transgenic mouse model of Huntington's disease. PloS One 2012;7:e41423.
Klevytska AM, Tebbenkamp AT, Savonenko AV, Borchelt DR. Partial depletion of CREB-binding protein reduces life expectancy in a mouse model of Huntington disease. J Neuropathol Exp Neurol 2010;69:396–404.
Taylor JP, Taye AA, Campbell C, Kazemi-Esfarjani P, Fischbeck KH, Min KT. Aberrant histone acetylation, altered transcription, and retinal degeneration in a Drosophila model of polyglutamine disease are rescued by CREB-binding protein. Genes Develop 2003;17:1463–1468.
Dompierre JP, Godin JD, Charrin BC, et al. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J Neurosci 2007;27:3571–3583.
Ferrante RJ, Kubilus JK, Lee J, et al. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J Neurosci 2003;23:9418–9427.
Gardian G, Browne SE, Choi DK, et al. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease. J Biol Chem 2005;280:556–563.
Goedert M, Spillantini MG, Del Tredici K, Braak H. 100 years of Lewy pathology. Nat Rev Neurol 2013;9:13–24.
Yasuda T, Mochizuki H. The regulatory role of alpha-synuclein and parkin in neuronal cell apoptosis; possible implications for the pathogenesis of Parkinson's disease. Apoptosis 2010;15:1312–1321.
Kontopoulos E, Parvin JD, Feany MB. Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 2006;15:3012–3023.
Chen PS, Peng GS, Li G, et al. Valproate protects dopaminergic neurons in midbrain neuron/glia cultures by stimulating the release of neurotrophic factors from astrocytes. Mol Psychiatry 2006;11:1116–1125.
Chen PS, Wang CC, Bortner CD, et al. Valproic acid and other histone deacetylase inhibitors induce microglial apoptosis and attenuate lipopolysaccharide-induced dopaminergic neurotoxicity. Neuroscience 2007;149:203–212.
Gardian G, Yang L, Cleren C, Calingasan NY, Klivenyi P, Beal MF. Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. Neuromol Med 2004;5:235–241.
Gottlicher M, Minucci S, Zhu P, et al. Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 2001;20:6969–6978.
Monti B, Gatta V, Piretti F, Raffaelli SS, Virgili M, Contestabile A. Valproic acid is neuroprotective in the rotenone rat model of Parkinson's disease: involvement of alpha-synuclein. Neurotox Res 2010;17:130–141.
Outeiro TF, Kontopoulos E, Altmann SM, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science 2007;317:516–519.
Song C, Kanthasamy A, Anantharam V, Sun F, Kanthasamy AG. Environmental neurotoxic pesticide increases histone acetylation to promote apoptosis in dopaminergic neuronal cells: relevance to epigenetic mechanisms of neurodegeneration. Mol Pharmacol 2010;77:621–632.
Jin H, Kanthasamy A, Ghosh A, Yang Y, Anantharam V, Kanthasamy AG. alpha-Synuclein negatively regulates protein kinase Cdelta expression to suppress apoptosis in dopaminergic neurons by reducing p300 histone acetyltransferase activity. J Neurosci 2011;31:2035–2051.
Turner MR, Hardiman O, Benatar M, et al. Controversies and priorities in amyotrophic lateral sclerosis. Lancet Neurol 2013;12:310–322.
Mackenzie IR, Bigio EH, Ince PG, et al. Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 2007;61:427–434.
Deng HX, Zhai H, Bigio EH, et al. FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann Neurol 2010;67:739–748.
Dupuis L, Pradat PF, Ludolph AC, Loeffler JP. Energy metabolism in amyotrophic lateral sclerosis. Lancet Neurol 2011;10:75–82.
Gibson SB, Bromberg MB. Amyotrophic lateral sclerosis: drug therapy from the bench to the bedside. Semin Neurol 2012;32:173–178.
Ilieva H, Polymenidou M, Cleveland DW. Non-cell autonomous toxicity in neurodegenerative disorders: ALS and beyond. J Cell Biol 2009;187:761–772.
Dupuis L, Loeffler JP. Neuromuscular junction destruction during amyotrophic lateral sclerosis: insights from transgenic models. Curr Opin Pharmacol 2009;9:341–346.
Jiang YM, Yamamoto M, Kobayashi Y, et al. Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. Ann Neurol 2005;57:236–251.
Janssen C, Schmalbach S, Boeselt S, Sarlette A, Dengler R, Petri S. Differential histone deacetylase mRNA expression patterns in amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 2010;69:573–581.
Ryu H, Smith K, Camelo SI, et al. Sodium phenylbutyrate prolongs survival and regulates expression of anti-apoptotic genes in transgenic amyotrophic lateral sclerosis mice. J Neurochem 2005;93:1087–1098.
Sugai F, Yamamoto Y, Miyaguchi K, et al. Benefit of valproic acid in suppressing disease progression of ALS model mice. Eur J Neurosci 2004;20:3179–3183.
Petri S, Kiaei M, Kipiani K, et al. Additive neuroprotective effects of a histone deacetylase inhibitor and a catalytic antioxidant in a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 2006;22:40–49.
Del Signore SJ, Amante DJ, Kim J, et al. Combined riluzole and sodium phenylbutyrate therapy in transgenic amyotrophic lateral sclerosis mice. Amyotroph Lateral Scler 2009;10:85–94.
Rouaux C, Panteleeva I, Rene F, et al. Sodium valproate exerts neuroprotective effects in vivo through CREB-binding protein-dependent mechanisms but does not improve survival in an amyotrophic lateral sclerosis mouse model. J Neurosci 2007;27:5535–5545.
De Vos KJ, Chapman AL, Tennant ME, et al. Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content. Hum Mol Genet 2007;16:2720–2728.
Creppe C, Malinouskaya L, Volvert ML, et al. Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell 2009;136:551–564.
Simpson CL, Lemmens R, Miskiewicz K, et al. Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Hum Mol Genet 2009;18:472–481.
Taes I, Timmers M, Hersmus N, et al. Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS. Hum Mol Genet 2013;22:1783–1790.
Gal J, Chen J, Barnett KR, Yang L, Brumley E, Zhu H. HDAC6 regulates mutant SOD1 aggregation through two SMIR motifs and tubulin acetylation. J Biol Chem 2013;288:15035–15045.
Miskiewicz K, Jose LE, Bento-Abreu A, et al. ELP3 controls active zone morphology by acetylating the ELKS family member Bruchpilot. Neuron 2011;72:776–788.
Roy S, Tenniswood M. Site-specific acetylation of p53 directs selective transcription complex assembly. J Biol Chem 2007;282:4765–4771.
Martin LJ, Liu Z. DNA damage profiling in motor neurons: a single-cell analysis by comet assay. Neurochem Res 2002;27:1093–1104.
Barbosa LF, Cerqueira FM, Macedo AF, et al. Increased SOD1 association with chromatin, DNA damage, p53 activation, and apoptosis in a cellular model of SOD1-linked ALS. Biochim Biophys Acta 2010;1802:462–471.
Gonzalez de Aguilar JL, Gordon JW, Rene F, et al. Alteration of the Bcl-x/Bax ratio in a transgenic mouse model of amyotrophic lateral sclerosis: evidence for the implication of the p53 signaling pathway. Neurobiol Dis 2000;7:406–415.
Di Giovanni S, Knights CD, Rao M, et al. The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 2006;25:4084–4096.
Pearson M, Carbone R, Sebastiani C, et al. PML regulates p53 acetylation and premature senescence induced by oncogenic Ras. Nature 2000;406:207–210.
Kim D, Nguyen MD, Dobbin MM, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. EMBO J 2007;26:3169–3179.
Boillee S, Vande Velde C, Cleveland DW. ALS: a disease of motor neurons and their nonneuronal neighbors. Neuron 2006;52:39–59.
Mejat A, Ramond F, Bassel-Duby R, Khochbin S, Olson EN, Schaeffer L. Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression. Nat Neurosci 2005;8:313–321.
Ravel-Chapuis A, Vandromme M, Thomas JL, Schaeffer L. Postsynaptic chromatin is under neural control at the neuromuscular junction. EMBO J 2007;26:1117–1128.
Selkoe DJ. Preventing Alzheimer's disease. Science 2012;337:1488–1492.
Hardy JA, Higgins GA. Alzheimer's disease: the amyloid cascade hypothesis. Science 1992;256:184–185.
Iqbal K, Liu F, Gong CX, Alonso Adel C, Grundke-Iqbal I. Mechanisms of tau-induced neurodegeneration. Acta Neuropathol 2009;118:53–69.
Davies P, Maloney AJ. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976;2:1403.
Bettens K, Sleegers K, Van Broeckhoven C. Genetic insights in Alzheimer's disease. Lancet Neurol 2013;12:92–104.
Adwan L, Zawia NH. Epigenetics: A novel therapeutic approach for the treatment of Alzheimer's disease. Pharmacol Therap 2013;139:41–50.
Albrecht S, Bourdeau M, Bennett D, Mufson EJ, Bhattacharjee M, LeBlanc AC. Activation of caspase-6 in aging and mild cognitive impairment. Am J Pathol 2007;170:1200–1209.
Guo H, Albrecht S, Bourdeau M, Petzke T, Bergeron C, LeBlanc AC. Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease. Am J Pathol 2004;165:523–531.
Guo H, Petrin D, Zhang Y, Bergeron C, Goodyer CG, LeBlanc AC. Caspase-1 activation of caspase-6 in human apoptotic neurons. Cell Death Differ 2006;13:285–292.
Saura CA, Choi SY, Beglopoulos V, et al. Loss of presenilin function causes impairments of memory and synaptic plasticity followed by age-dependent neurodegeneration. Neuron 2004;42:23–36.
Francis YI, Diss JK, Kariti M, Stephanou A, Latchman DS. p300 activation by Presenilin 1 but not by its M146L mutant. Neurosci Lett 2007;413:137–140.
Francis YI, Stephanou A, Latchman DS. CREB-binding protein activation by presenilin 1 but not by its M146L mutant. Neuroreport 2006;17:917–921.
Marambaud P, Wen PH, Dutt A, et al. A CBP binding transcriptional repressor produced by the PS1/epsilon-cleavage of N-cadherin is inhibited by PS1 FAD mutations. Cell 2003;114:635–645.
Caccamo A, Maldonado MA, Bokov AF, Majumder S, Oddo S. CBP gene transfer increases BDNF levels and ameliorates learning and memory deficits in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 2010;107:22687–22692.
Liu R, Lei JX, Luo C, et al. Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's disease. Neurobiol Dis 2012;45:902–912.
Duclot F, Meffre J, Jacquet C, Gongora C, Maurice T. Mice knock out for the histone acetyltransferase p300/CREB binding protein-associated factor develop a resistance to amyloid toxicity. Neuroscience 2010;167:850–863.
Ricobaraza A, Cuadrado-Tejedor M, Garcia-Osta A. Long-term phenylbutyrate administration prevents memory deficits in Tg2576 mice by decreasing Abeta. Front Biosci (Elite Ed) 2011;3:1375–1384.
Ricobaraza A, Cuadrado-Tejedor M, Marco S, Perez-Otano I, Garcia-Osta A. Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus 2012;22:1040–1050.
Ricobaraza A, Cuadrado-Tejedor M, Perez-Mediavilla A, Frechilla D, Del Rio J, Garcia-Osta A. Phenylbutyrate ameliorates cognitive deficit and reduces tau pathology in an Alzheimer's disease mouse model. Neuropsychopharmacology 2009;34:1721–1732.
Min SW, Cho SH, Zhou Y, et al. Acetylation of tau inhibits its degradation and contributes to tauopathy. Neuron 2010;67:953–966.
Irwin DJ, Cohen TJ, Grossman M, et al. Acetylated tau, a novel pathological signature in Alzheimer's disease and other tauopathies. Brain 2012;135:807–818.
Cohen TJ, Friedmann D, Hwang AW, Marmorstein R, Lee VM. The microtubule-associated tau protein has intrinsic acetyltransferase activity. Nat Struct Mol Biol 2013;20:756–762.
Mackenzie IR, Baker M, Pickering-Brown S, et al. The neuropathology of frontotemporal lobar degeneration caused by mutations in the progranulin gene. Brain 2006;129:3081–3090.
Cenik B, Sephton CF, Dewey CM, et al. Suberoylanilide hydroxamic acid (vorinostat) up-regulates progranulin transcription: rational therapeutic approach to frontotemporal dementia. J Biol Chem 2011;286:16101–16108.
Odagiri S, Tanji K, Mori F, et al. Brain expression level and activity of HDAC6 protein in neurodegenerative dementia. Biochem Biophys Res Commun 2013;430:394–399.
Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003;115:727–738.
Miki Y, Mori F, Tanji K, Kakita A, Takahashi H, Wakabayashi K. Accumulation of histone deacetylase 6, an aggresome-related protein, is specific to Lewy bodies and glial cytoplasmic inclusions. Neuropathology 2011;31:561–568.
Agranoff BW. Memory and protein synthesis. Sci Am 1967;216:115–122.
Flood JF, Rosenzweig MR, Bennett EL, Orme AE. The influence of duration of protein synthesis inhibition on memory. Physiol Behav 1973;10:555–562.
Nguyen PV, Abel T, Kandel ER. Requirement of a critical period of transcription for induction of a late phase of LTP. Science 1994;265:1104–1107.
Stanton PK, Sarvey JM. Blockade of long-term potentiation in rat hippocampal CA1 region by inhibitors of protein synthesis. J Neurosci 1984;4:3080–3088.
Gutierrez H, Davies AM. Regulation of neural process growth, elaboration and structural plasticity by NF-kappaB. Trends Neurosci 2011;34:316–325.
Sakamoto K, Karelina K, Obrietan K. CREB: a multifaceted regulator of neuronal plasticity and protection. J Neurochem 2011;116:1–9.
Graff J, Tsai LH. Histone acetylation: molecular mnemonics on the chromatin. Nat Rev Neurosci 2013;14:97–111.
Peixoto L, Abel T. The role of histone acetylation in memory formation and cognitive impairments. Neuropsychopharmacology 2013;38:62–76.
Zocchi L, Sassone-Corsi P. Joining the dots: from chromatin remodeling to neuronal plasticity. Curr Opin Neurobiol 2010;20:432–440.
Levenson JM, O'Riordan KJ, Brown KD, Trinh MA, Molfese DL, Sweatt JD. Regulation of histone acetylation during memory formation in the hippocampus. J Biol Chem 2004;279:40545–40559.
Bousiges O, Vasconcelos AP, Neidl R, et al. Spatial memory consolidation is associated with induction of several lysine-acetyltransferase (histone acetyltransferase) expression levels and H2B/H4 acetylation-dependent transcriptional events in the rat hippocampus. Neuropsychopharmacology 2010;35:2521–2537.
Calfa G, Chapleau CA, Campbell S, et al. HDAC activity is required for BDNF to increase quantal neurotransmitter release and dendritic spine density in CA1 pyramidal neurons. Hippocampus 2012;22:1493–1500.
Bousiges O, Neidl R, Majchrzak M, et al. Detection of Histone acetylation levels in the dorsal hippocampus reveals early tagging on specific residues of H2B and H4 histones in response to learning. PloS One 2013;8:e57816.
Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009;459:55–60.
McQuown SC, Barrett RM, Matheos DP, et al. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci 2011;31:764–774.
Bahari-Javan S, Maddalena A, Kerimoglu C, et al. HDAC1 regulates fear extinction in mice. J Neurosci 2012;32:5062–5073.
Agis-Balboa RC, Pavelka Z, Kerimoglu C, Fischer A. Loss of HDAC5 impairs memory function: implications for Alzheimer's disease. J Alzheimers Dis 2013;33:35–44.
Kim MS, Akhtar MW, Adachi M, et al. An essential role for histone deacetylase 4 in synaptic plasticity and memory formation. J Neurosci 2012;32:10879–10886.
Monsey MS, Ota KT, Akingbade IF, Hong ES, Schafe GE. Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PloS One 2011;6:e19958.
Zhang X, Yuan Z, Zhang Y, et al. HDAC6 modulates cell motility by altering the acetylation level of cortactin. Mol Cell 2007;27:197–213.
Zhang Y, Zhang M, Dong H, et al. Deacetylation of cortactin by SIRT1 promotes cell migration. Oncogene 2009;28:445–460.
Catarino T, Ribeiro L, Santos SD, Carvalho AL. Regulation of synapse composition by protein acetylation: the role of acetylated cortactin. J Cell Sc 2013;126:149–162.
Alberini CM. Transcription factors in long-term memory and synaptic plasticity. Physiol Rev 2009;89:121–145.
Mattson MP, Meffert MK. Roles for NF-kappaB in nerve cell survival, plasticity, and disease. Cell Death Differ 2006;13:852–860.
Chen LF, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB. EMBO J 2002;21:6539–6548.
Chen L, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science 2001;293:1653–1657.
Yeh SH, Lin CH, Gean PW. Acetylation of nuclear factor-kappaB in rat amygdala improves long-term but not short-term retention of fear memory. Mol Pharmacol 2004;65:1286–1292.
Nasca C, Xenos D, Barone Y, et al. L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A 2013;110:4804–4809.
Valor LM, Viosca J, Lopez-Atalaya JP, Barco A. Lysine acetyltransferases CBP and p300 as therapeutic targets in cognitive and neurodegenerative disorders. Curr Pharm Design 2013 Feb 19 [Epub ahead of print].
Alarcon JM, Malleret G, Touzani K, et al. Chromatin acetylation, memory, and LTP are impaired in CBP+/− mice: a model for the cognitive deficit in Rubinstein-Taybi syndrome and its amelioration. Neuron 2004;42:947–959.
Bourtchouladze R, Lidge R, Catapano R, et al. A mouse model of Rubinstein-Taybi syndrome: defective long-term memory is ameliorated by inhibitors of phosphodiesterase 4. Proc Natl Acad Sci U S A 2003;100:10518–10522.
Korzus E, Rosenfeld MG, Mayford M. CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 2004;42:961–972.
Wood MA, Kaplan MP, Park A, et al. Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage. Learn Mem 2005;12:111–119.
Chen G, Zou X, Watanabe H, van Deursen JM, Shen J. CREB binding protein is required for both short-term and long-term memory formation. J Neurosci 2010;30:13066–13077.
Valor LM, Pulopulos MM, Jimenez-Minchan M, Olivares R, Lutz B, Barco A. Ablation of CBP in forebrain principal neurons causes modest memory and transcriptional defects and a dramatic reduction of histone acetylation but does not affect cell viability. J Neurosci 2011;31:1652–1663.
Barrett RM, Malvaez M, Kramar E, et al. Hippocampal focal knockout of CBP affects specific histone modifications, long-term potentiation, and long-term memory. Neuropsychopharmacology 2011;36:1545–1556.
Oliveira AM, Wood MA, McDonough CB, Abel T. Transgenic mice expressing an inhibitory truncated form of p300 exhibit long-term memory deficits. Learning Memory 2007;14:564–572.
Oliveira AM, Estevez MA, Hawk JD, Grimes S, Brindle PK, Abel T. Subregion-specific p300 conditional knock-out mice exhibit long-term memory impairments. Learn Mem 2011;18:161–169.
Maurice T, Duclot F, Meunier J, et al. Altered memory capacities and response to stress in p300/CBP-associated factor (PCAF) histone acetylase knockout mice. Neuropsychopharmacology 2008;33:1584–1602.
Bartholdi D, Roelfsema JH, Papadia F, et al. Genetic heterogeneity in Rubinstein-Taybi syndrome: delineation of the phenotype of the first patients carrying mutations in EP300. J Med Genet 2007;44:327–333.
Roelfsema JH, White SJ, Ariyurek Y, et al. Genetic heterogeneity in Rubinstein-Taybi syndrome: mutations in both the CBP and EP300 genes cause disease. Am J Hum Genet 2005;76:572–580.
Viosca J, Lopez-Atalaya JP, Olivares R, Eckner R, Barco A. Syndromic features and mild cognitive impairment in mice with genetic reduction on p300 activity: Differential contribution of p300 and CBP to Rubinstein-Taybi syndrome etiology. Neurobiol Dis 2010;37:186–194.
Hallam TM, Bourtchouladze R. Rubinstein-Taybi syndrome: molecular findings and therapeutic approaches to improve cognitive dysfunction. Cell Mol Life Sci 2006;63:1725–1735.
McQuown SC, Wood MA. HDAC3 and the molecular brake pad hypothesis. Neurobiol Learn Mem 2011;96:27–34.
Graff J, Rei D, Guan JS, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012;483:222–226.
Vecsey CG, Hawk JD, Lattal KM, et al. Histone deacetylase inhibitors enhance memory and synaptic plasticity via CREB:CBP-dependent transcriptional activation. J Neurosci 2007;27:6128–6140.
Dancy BM, Crump NT, Peterson DJ, et al. Live-cell studies of p300/CBP histone acetyltransferase activity and inhibition. Chembiochem 2012;13:2113–2121.
Hazzalin CA, Mahadevan LC. Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun. PLoS Biol 2005;3:e393.
Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007;26:5541–5552.
Wei W, Coelho CM, Li X, et al. p300/CBP-associated factor selectively regulates the extinction of conditioned fear. J Neurosci 2012;32:11930–11941.
Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M. Histone modifications around individual BDNF gene promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem 2007;14:268–276.
Lattal KM, Barrett RM, Wood MA. Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci 2007;121:1125–1131.
Stafford JM, Raybuck JD, Ryabinin AE, Lattal KM. Increasing histone acetylation in the hippocampus-infralimbic network enhances fear extinction. Biol Psychiatry 2012;72:25–33.
Benes FM. Searching for unique endophenotypes for schizophrenia and bipolar disorder within neural circuits and their molecular regulatory mechanisms. Schizophr Bull 2007;33:932–936.
Sharma RP, Grayson DR, Gavin DP. Histone deactylase 1 expression is increased in the prefrontal cortex of schizophrenia subjects: analysis of the National Brain Databank microarray collection. Schizophr Res 2008;98:111–117.
Ourednik J, Ourednik V, Lynch WP, Schachner M, Snyder EY. Neural stem cells display an inherent mechanism for rescuing dysfunctional neurons. Nat Biotechnol 2002;20:1103–1110.
Teng YD, Lavik EB, Qu X, et al. Functional recovery following traumatic spinal cord injury mediated by a unique polymer scaffold seeded with neural stem cells. Proc Natl Acad Sci U S A 2002;99:3024–3029.
Clement AM, Nguyen MD, Roberts EA, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice. Science 2003;302:113–117.
Carletti B, Piemonte F, Rossi F. Neuroprotection: the emerging concept of restorative neural stem cell biology for the treatment of neurodegenerative diseases. Curr Neuropharmacol 2011;9:313–317.
Rossi F, Cattaneo E. Opinion: neural stem cell therapy for neurological diseases: dreams and reality. Nature reviews Neurosci 2002;3:401–409.
Faure A, Verret L, Bozon B, et al. Impaired neurogenesis, neuronal loss, and brain functional deficits in the APPxPS1-Ki mouse model of Alzheimer's disease. Neurobiol Aging 2011;32:407–418.
Verret L, Jankowsky JL, Xu GM, Borchelt DR, Rampon C. Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. J Neurosci 2007;27:6771–6780.
Branchi I, Karpova NN, D'Andrea I, Castren E, Alleva E. Epigenetic modifications induced by early enrichment are associated with changes in timing of induction of BDNF expression. Neurosci Lett 2011;495:168–172.
Lopez-Atalaya JP, Ciccarelli A, Viosca J, et al. CBP is required for environmental enrichment-induced neurogenesis and cognitive enhancement. EMBO J 2011;30:4287–4298.
Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 2006;7:697–709.
O'Callaghan RM, Griffin EW, Kelly AM. Long-term treadmill exposure protects against age-related neurodegenerative change in the rat hippocampus. Hippocampus 2009;19:1019–1029.
Rossi C, Angelucci A, Costantin L, et al. Brain-derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci2006;24:1850–1856.
Simpson J, Kelly JP. The impact of environmental enrichment in laboratory rats--behavioural and neurochemical aspects. Behav Brain Res 2011;222:246–264.
Nithianantharajah J, Hannan AJ. Mechanisms mediating brain and cognitive reserve: experience-dependent neuroprotection and functional compensation in animal models of neurodegenerative diseases. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:331–339.
This work was supported by funding from the Centre National de la Recherche Scientifique (CNRS), the University of Strasbourg, the Department of Biotechnology, the Government of India (Grant/ DBT/ CSH/ GIA/ 1752 to TKK), the Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Agence Nationale de la Recherche (ANR-12-MALZ-0002-01 to ALB), the Indo-French Centre for the Promotion of Advanced Research (IFCPAR/CEFIPRA No.4803-3 to T.K. Kundu and A.L. Boutillier), and Alsace Alzheimer 67 association (to A.L. Boutillier and F. Blanc). T.K. Kundu is a recipient of the Sir JC Bose national fellowship from the Department of Science and Technology through the government of India. Raphaelle Cassel received a doctoral fellowship from the French government. A. Schneider was supported through the Agence Nationale pour la Recherche (ANR-12-MALZ-0002). Frédéric Blanc reports receiving personal fees from Eisai, Piramal, Biogen Novartis, Janssen, Lundbeck, Pfizer, and Biogen, and non-financial support from Novartis, Lundbeck, Bayer Schering, Merck Serono, TEVA Neurosciences, and Pfizer, outside of the submitted work. Amrutha Swaminathan reports receiving grants from the Council for Scientific and Industrial Research, outside of the submitted work. Anne L. Boutillier, S. Chatterjee, and T.K. Kundu have a patent HAT Activator CSP-TTK21 pending. Olivier Bousiges, R. Cassel, A. Schneider, and B.R. Selvi. have nothing to disclose.
Required Author Forms
Disclosure forms provided by the authors are available with the online version of this article.
Electronic supplementary material
Below is the link to the electronic supplementary material.
(PDF 1224 kb)
About this article
Cite this article
Schneider, A., Chatterjee, S., Bousiges, O. et al. Acetyltransferases (HATs) as Targets for Neurological Therapeutics. Neurotherapeutics 10, 568–588 (2013). https://doi.org/10.1007/s13311-013-0204-7
- HAT activator molecule
- Lysine acetylation
- CREB-binding protein
- Learning and memory
- Adult neurogenesis
- Neurodegenerative diseases