HDAC Inhibitors as Novel Therapeutics in Aging and Alzheimer's Disease

Epigenetic Regulation in the Nervous System

Volumn , Issue , 2013, Pages 225-248

  Nott, Alexi ^a   Fass, Daniel M ^b,c   Haggarty, Stephen J ^b,c   Tsai, Li Huei ^a,c  

^a HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c BROAD INSTITUTE OF MIT AND HARVARD   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84882686666     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-0-12-391494-1.00008-2     Document Type: Chapter

References (117)

1. Penner MR, Roth TL, Barnes CA, Sweatt JD An epigenetic hypothesis of aging-related cognitive dysfunction. Front Aging Neurosci 2010, 2:9.
2. Albert M, Duffy FH, Naeser M Nonlinear changes in cognition with age and their neuropsychologic correlates. Can J Psychol 1987, 41(2):141-157.
3. Craik FI, Moscovitch M, McDowd JM Contributions of surface and conceptual information to performance on implicit and explicit memory tasks. J Exp Psychol Learn Mem Cogn 1994, 20(4):864-875.
4. Zelinski EM, Burnight KP Sixteen-year longitudinal and time lag changes in memory and cognition in older adults. Psychol Aging 1997, 12(3):503-513.
5. Petersen RC, Smith G, Kokmen E, Ivnik RJ, Tangalos EG Memory function in normal aging. Neurology 1992, 42(2):396-401.
6. Loerch PM, Lu T, Dakin KA, et al. Evolution of the aging brain transcriptome and synaptic regulation. PLoS One 2008, 3(10):e3329.
7. Wang D, Xia X, Weiss RE, Refetoff S, Yen PM Distinct and histone-specific modifications mediate positive versus negative transcriptional regulation of TSHalpha promoter. PLoS One 2010, 5(3):e9853.
8. Burke SN, Barnes CA Neural plasticity in the ageing brain. Nat Rev Neurosci 2006, 7(1):30-40.
9. Davis HP, Squire LR Protein synthesis and memory: a review. Psychol Bull 1984, 96(3):518-559.
10. Frey U, Krug M, Reymann KG, Matthies H Anisomycin an inhibitor of protein synthesis, blocks late phases of LTP phenomena in the hippocampal CA1 region in vitro. Brain Res 1988, 452(1-2):57-65.
11. Kandel ER The molecular biology of memory storage: a dialog between genes and synapses. Biosci Rep 2001, 21(5):565-611.
12. Barco A, Lopez de Armentia M, Alarcon JM Synapse-specific stabilization of plasticity processes: the synaptic tagging and capture hypothesis revisited 10 years later. Neurosci Biobehav Rev 2008, 32(4):831-851.
13. Gold PE Protein synthesis inhibition and memory: formation vs amnesia. Neurobiol Learn Mem 2008, 89(3):201-211.
14. West AE, Greenberg ME Neuronal activity-regulated gene transcription in synapse development and cognitive function. Cold Spring Harb Perspect Biol 2011, 3(6):1-21.
15. Lu T, Pan Y, Kao SY, et al. Gene regulation and DNA damage in the ageing human brain. Nature 2004, 429(6994):883-891.
16. Berchtold NC, Cribbs DH, Coleman PD, et al. Gene expression changes in the course of normal brain aging are sexually dimorphic. Proc Natl Acad Sci USA 2008, 105(40):15605-15610.
17. Fraser HB, Khaitovich P, Plotkin JB, Paabo S, Eisen MB Aging and gene expression in the primate brain. PLoS Biol 2005, 3(9):e274.
18. Jiang CH, Tsien JZ, Schultz PG, Hu Y The effects of aging on gene expression in the hypothalamus and cortex of mice. Proc Natl Acad Sci USA 2001, 98(4):1930-1934.
19. Blalock EM, Chen KC, Sharrow K, et al. Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J Neurosci 2003, 23(9):3807-3819.
20. Xu X, Zhan M, Duan W, et al. Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender. Genome Biol 2007, 8(11):R234.
21. Verbitsky M, Yonan AL, Malleret G, Kandel ER, Gilliam TC, Pavlidis P Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice. Learn Mem 2004, 11(3):253-260.
22. Penner MR, Roth TL, Chawla MK, et al. Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol Aging 2011, 32(12):2198-2210.
23. Blalock EM, Geddes JW, Chen KC, Porter NM, Markesbery WR, Landfield PW Incipient Alzheimer's disease: microarray correlation analyses reveal major transcriptional and tumor suppressor responses. Proc Natl Acad Sci USA 2004, 101(7):2173-2178.
24. Small SA, Kent K, Pierce A, et al. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann Neurol 2005, 58(6):909-919.
25. Blalock EM, Buechel HM, Popovic J, Geddes JW, Landfield PW Microarray analyses of laser-captured hippocampus reveal distinct gray and white matter signatures associated with incipient Alzheimer's disease. J Chem Neuroanat 2011, 42(2):118-126.
26. Fischer A, Sananbenesi F, Pang PT, Lu B, Tsai LH Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory. Neuron 2005, 48(5):825-838.
27. Graff J, Rei D, Guan JS, et al. An epigenetic blockade of cognitive functions in the neurodegenerating brain. Nature 2012, 483(7388):222-226.
28. Kim D, Frank CL, Dobbin MM, et al. Deregulation of HDAC1 by p25/Cdk5 in Neurotoxicity. Neuron 2008, 60(5):803-817.
29. Suganuma T, Workman JL Signals and combinatorial functions of histone modifications. Annu Rev Biochem 2011, 80:473-499.
30. 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(39):40545-40559.
31. Fontan-Lozano A, Romero-Granados R, Troncoso J, Munera A, Delgado-Garcia JM, Carrion AM Histone deacetylase inhibitors improve learning consolidation in young and in KA-induced-neurodegeneration and SAMP-8-mutant mice. Mol Cell Neurosci 2008, 39(2):193-201.
32. 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(4):268-276.
33. Ito H, Yoshimura N, Kurosawa M, Ishii S, Nukina N, Okazawa H Knock-down of PQBP1 impairs anxiety-related cognition in mouse. Hum Mol Genet 2009, 18(22):4239-4254.
34. Maddox SA, Schafe GE Epigenetic alterations in the lateral amygdala are required for reconsolidation of a Pavlovian fear memory. Learn Mem 2011, 18(9):579-593.
35. 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(5):e19958.
36. Fischer A, Sananbenesi F, Wang X, Dobbin M, Tsai L-H Recovery of learning and memory is associated with chromatin remodelling. Nature 2007, 447(7141):178-182.
37. Koseki T, Mouri A, Mamiya T, et al. Exposure to enriched environments during adolescence prevents abnormal behaviours associated with histone deacetylation in phencyclidine-treated mice. Int J Neuropsychopharmacol 2011, 1-13.
38. Peleg S, Sananbenesi F, Zovoilis A, et al. Altered histone acetylation is associated with age-dependent memory impairment in mice. Science 2010, 328(5979):753-756.
39. Radde R, Bolmont T, Kaeser SA, et al. Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep 2006, 7(9):940-946.
40. Gengler S, Hamilton A, Holscher C Synaptic plasticity in the hippocampus of a APP/PS1 mouse model of Alzheimer's disease is impaired in old but not young mice. PLoS One 2010, 5(3):e9764.
41. Francis YI, Fa M, Ashraf H, et al. Dysregulation of histone acetylation in the APP/PS1 mouse model of Alzheimer's disease. J Alzheimers Dis 2009, 18(1):131-139.
42. Zeng Y, Tan M, Kohyama J, et al. Epigenetic enhancement of BDNF signaling rescues synaptic plasticity in aging. J Neurosci 2011, 31(49):17800-17810.
43. Kontopoulos E, Parvin JD, Feany MB Alpha-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity. Hum Mol Genet 2006, 15(20):3012-3023.
44. 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(6):1203-1216.
45. 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(7):1721-1732.
46. Govindarajan N, Agis-Balboa RC, Walter J, Sananbenesi F, Fischer A Sodium butyrate improves memory function in an Alzheimer's disease mouse model when administered at an advanced stage of disease progression. J Alzheimers Dis 2011, 26(1):187-197.
47. 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(24):6537-6549.
48. Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009, 459(7243):55-60.
49. McQuown SC, Barrett RM, Matheos DP, et al. HDAC3 is a critical negative regulator of long-term memory formation. J Neurosci 2011, 31(2):764-774.
50. Fischer A, Sananbenesi F, Mungenast A, Tsai LH Targeting the correct HDAC(s) to treat cognitive disorders. Trends Pharmacol Sci 2010, 31(12):605-617.
51. Haggarty SJ, Tsai LH Probing the role of HDACs and mechanisms of chromatin-mediated neuroplasticity. Neurobiol Learn Mem 2011, 96(1):41-52.
52. Graff J, Kim D, Dobbin MM, Tsai LH Epigenetic regulation of gene expression in physiological and pathological brain processes. Physiol Rev 2011, 91(2):603-649.
53. Stilling RM, Fischer A The role of histone acetylation in age-associated memory impairment and Alzheimer's disease. Neurobiol Learn Mem 2011, 96(1):19-26.
54. Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009, 459(7243):55-60.
55. 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(13):3169-3179.
56. Bahari-Javan S, Maddalena A, Kerimoglu C, et al. HDAC1 regulates fear extinction in mice. J Neurosci 2012, 32(15):5062-5073.
57. Gao J, Wang WY, Mao YW, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 2010, 466(7310):1105-1109.
58. Finnin MS, Donigian JR, Cohen A, et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999, 401(6749):188-193.
59. Vannini A, Volpari C, Filocamo G, et al. Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc Natl Acad Sci USA 2004, 101(42):15064-15069.
60. Sternson SM, Wong JC, Grozinger CM, Schreiber SL Synthesis of 7200 small molecules based on a substructural analysis of the histone deacetylase inhibitors trichostatin and trapoxin. Organic letters 2001, 3(26):4239-4242.
61. Bressi JC, Jennings AJ, Skene R, et al. Exploration of the HDAC2 foot pocket: synthesis and SAR of substituted N-(2-aminophenyl)benzamides. Bioorg Med Chem Lett 2010, 20(10):3142-3145.
62. Kilgore M, Miller CA, Fass DM, et al. Inhibitors of class 1 histone deacetylases reverse contextual memory deficits in a mouse model of Alzheimer's disease. Neuropsychopharmacology 2010, 35(4):870-880.
63. Fass DM, Shah R, Ghosh B, et al. Effect of inhibiting histone deacetylase with short-chain carboxylic acids and their hydroxamic acid analogs on vertebrate development and neuronal chromatin. ACS Med Chem Lett 2010, 2(1):39-42.
64. Bradner JE, Mak R, Tanguturi SK, et al. Chemical genetic strategy identifies histone deacetylase 1 (HDAC1) and HDAC2 as therapeutic targets in sickle cell disease. Proc Natl Acad Sci USA 2010, 107(28):12617-12622.
65. Chou CJ, Herman D, Gottesfeld JM Pimelic diphenylamide 106 is a slow, tight-binding inhibitor of class I histone deacetylases. J Biol Chem 2008, 283(51):35402-35409.
66. Cornford EM, Diep CP, Pardridge WM Blood-brain barrier transport of valproic acid. J Neurochem 1985, 44(5):1541-1550.
67. Murphy KJ, Fox GB, Foley AG, et al. Pentyl-4-yn-valproic acid enhances both spatial and avoidance learning, and attenuates age-related NCAM-mediated neuroplastic decline within the rat medial temporal lobe. J Neurochem 2001, 78(4):704-714.
68. 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(28):9418-9427.
69. Hockly E, Richon VM, Woodman B, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl Acad Sci USA 2003, 100(4):2041-2046.
70. Korzus E, Rosenfeld MG, Mayford M CBP histone acetyltransferase activity is a critical component of memory consolidation. Neuron 2004, 42(6):961-972.
71. Hooker JM, Kim SW, Alexoff D, et al. Histone deacetylase inhibitor, MS-275, exhibits poor brain penetration: PK studies of [C]MS-275 using Positron emission tomography. ACS Chem Neurosci 2010, 1(1):65-73.
72. Hawk JD, Florian C, Abel T Post-training intrahippocampal inhibition of class I histone deacetylases enhances long-term object-location memory. Learn Mem 2011, 18(6):367-370.
73. 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):1-8.
74. Malvaez M, Sanchis-Segura C, Vo D, Lattal KM, Wood MA Modulation of chromatin modification facilitates extinction of cocaine-induced conditioned place preference. Biol Psychiatry 2010, 67(1):36-43.
75. Roozendaal B, Hernandez A, Cabrera SM, et al. Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification. J Neurosci 2010, 30(14):5037-5046.
76. Ferland CL, Schrader LA Regulation of histone acetylation in the hippocampus of chronically stressed rats: a potential role of sirtuins. Neuroscience 2011, 174:104-114.
77. Pastor V, Host L, Zwiller J, Bernabeu R Histone deacetylase inhibition decreases preference without affecting aversion for nicotine. J Neurochem 2011, 116(4):636-645.
78. Dash PK, Orsi SA, Zhang M, et al. Valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats. PLoS One 2010, 5(6):e11383.
79. 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(23):6128-6140.
80. Tian F, Marini AM, Lipsky RH Effects of histone deacetylase inhibitor Trichostatin A on epigenetic changes and transcriptional activation of Bdnf promoter 1 by rat hippocampal neurons. Ann N Y Acad Sci 2010, 1199:186-193.
81. 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(6):947-959.
82. Covington HE, Maze I, LaPlant QC, et al. Antidepressant actions of histone deacetylase inhibitors. J Neurosci 2009, 29(37):11451-11460.
83. Crawley JN What's Wrong with my Mouse? Behavioral Phenotyping of Transgenic and Knockout Mice 2007, Wiley-Interscience, Hoboken, NJ. 2nd ed.
84. Miller CA, Campbell SL, Sweatt JD DNA methylation and histone acetylation work in concert to regulate memory formation and synaptic plasticity. Neurobiol Learn Mem 2008, 89(4):599-603.
85. Lattal KM, Barrett RM, Wood MA Systemic or intrahippocampal delivery of histone deacetylase inhibitors facilitates fear extinction. Behav Neurosci 2007, 121(5):1125-1131.
86. Stefanko DP, Barrett RM, Ly AR, Reolon GK, Wood MA Modulation of long-term memory for object recognition via HDAC inhibition. Proc Natl Acad Sci USA 2009, 106(23):9447-9452.
87. Haettig J, Stefanko DP, Multani ML, Figueroa DX, McQuown SC, Wood MA HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner. Learn Mem 2011, 18(2):71-79.
88. Reolon GK, Maurmann N, Werenicz A, et al. Posttraining systemic administration of the histone deacetylase inhibitor sodium butyrate ameliorates aging-related memory decline in rats. Behav Brain Res 2011, 221(1):329-332.
89. Sharma B, Singh N Attenuation of vascular dementia by sodium butyrate in streptozotocin diabetic rats. Psychopharmacology (Berl) 2011, 215(4):677-687.
90. Ricobaraza A, Cuadrado-Tejedor M, Marco S, Pérez-Otaño I, García-Osta A Phenylbutyrate rescues dendritic spine loss associated with memory deficits in a mouse model of Alzheimer disease. Hippocampus 2012, 22(5):1040-1050.
91. 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.
92. Bredy TW, Barad M The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and reconsolidation of conditioned fear. Learn Mem 2008, 15(1):39-45.
93. Li S, Murakami Y, Wang M, Maeda K, Matsumoto K The effects of chronic valproate and diazepam in a mouse model of posttraumatic stress disorder. Pharmacol Biochem Behav 2006, 85(2):324-331.
94. O'Loinsigh ED, Gherardini LM, Gallagher HC, Foley AG, Murphy KJ, Regan CM Differential enantioselective effects of pentyl-4-yn-valproate on spatial learning in the rat, and neurite outgrowth and cyclin D3 expression in vitro. J Neurochem 2004, 88(2):370-379.
95. 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(5):1286-1292.
96. 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(5):1040-1050.
97. Rattray I, Scullion GA, Soulby A, Kendall DA, Pardon MC The occurrence of a deficit in contextual fear extinction in adult amyloid-over-expressing TASTPM mice is independent of the strength of conditioning but can be prevented by mild novel cage stress. Behav Brain Res 2009, 200(1):83-90.
98. Rattray I, Pitiot A, Lowe J, et al. Novel cage stress alters remote contextual fear extinction and regional T2 magnetic resonance relaxation times in TASTPM mice overexpressing amyloid. J Alzheimers Dis 2010, 20(4):1049-1068.
99. Bonardi C, de Pulford F, Jennings D, Pardon MC A detailed analysis of the early context extinction deficits seen in APPswe/PS1dE9 female mice and their relevance to preclinical Alzheimer's disease. Behav Brain Res 2011, 222(1):89-97.
100. Morris RGM Spatial localization does not require the presence of local cues. Learn Motivat 1981, 12(2):239-260.
101. Morris R Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984, 11(1):47-60.
102. Gallagher M, Burwell R, Burchinal M Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. Behav Neurosci 1993, 107(4):618-626.
103. Chouinard ML, Gallagher M, Yasuda RP, Wolfe BB, McKinney M Hippocampal muscarinic receptor function in spatial learning-impaired aged rats. Neurobiol Aging 1995, 16(6):955-963.
104. Geinisman Y, Ganeshina O, Yoshida R, Berry RW, Disterhoft JF, Gallagher M Aging, spatial learning, and total synapse number in the rat CA1 stratum radiatum. Neurobiol Aging 2004, 25(3):407-416.
105. Moran PM, Higgins LS, Cordell B, Moser PC Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein. Proc Natl Acad Sci USA 1995, 92(12):5341-5345.
106. D'Hooge R, Nagels G, Westland CE, Mucke L, De Deyn PP Spatial learning deficit in mice expressing human 751-amino acid beta-amyloid precursor protein. Neuroreport 1996, 7(15-17):2807-2811.
107. Hsiao K, Chapman P, Nilsen S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 1996, 274(5284):99-102.
108. Hsiao KK, Borchelt DR, Olson K, et al. Age-related CNS disorder and early death in transgenic FVB/N mice overexpressing Alzheimer amyloid precursor proteins. Neuron 1995, 15(5):1203-1218.
109. Foley AG, Gallagher HC, Murphy KJ, Regan CM Pentyl-4-yn-valproic acid reverses age-associated memory impairment in the Wistar rat. Neurobiol Aging 2004, 25(4):539-546.
110. Butterfield DA, Poon HF The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease. Exp Gerontol 2005, 40(10):774-783.
111. Ding H, Dolan PJ, Johnson GV Histone deacetylase 6 interacts with the microtubule-associated protein tau. J Neurochem 2008, 106(5):2119-2130.
112. Cook C, Gendron TF, Scheffel K, et al. Loss of HDAC6, a novel CHIP substrate, alleviates abnormal tau accumulation. Hum Mol Genet 2012, 21(13):2936-2945.
113. Glozak MA, Sengupta N, Zhang X, Seto E Acetylation and deacetylation of non-histone proteins. Gene 2005, 363:15-23.
114. Lahm A, Paolini C, Pallaoro M, et al. Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc Natl Acad Sci USA 2007, 104(44):17335-17340.
115. Bantscheff M, Hopf C, Savitski MM, et al. Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. Nat Biotechnol 2011, 29(3):255-265.
116. Smith KT, Martin-Brown SA, Florens L, Washburn MP, Workman JL Deacetylase inhibitors dissociate the histone-targeting ING2 subunit from the Sin3 complex. Chem Biol 2010, 17(1):65-74.
117. Itzhak Y, Anderson KL, Kelley JB, Petkov M Histone acetylation rescues contextual fear conditioning in nNOS KO mice and accelerates extinction of cued fear conditioning in wild type mice. Neurobiol Learn Mem 2012, 97:409-417.