The promise and perils of HDAC inhibitors in neurodegeneration

Annals of Clinical and Translational Neurology

Volumn 2, Issue 1, 2015, Pages 79-101

  Didonna, Alessandro ^a   Opal, Puneet ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ESTROGEN RECEPTOR; FRAGILE X MENTAL RETARDATION PROTEIN; FRATAXIN; HEAT SHOCK PROTEIN 90; HISTONE DEACETYLASE; HISTONE DEACETYLASE 10; HISTONE DEACETYLASE 4; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; MYOCYTE ENHANCER FACTOR 2; MYOD PROTEIN; NUCLEAR RECEPTOR COREPRESSOR; PROTEIN P53; RETINOBLASTOMA PROTEIN; SILENT INFORMATION REGULATOR PROTEIN 2; SIRTUIN 1; SURVIVAL MOTOR NEURON PROTEIN; TATA BINDING PROTEIN; THYROID HORMONE RECEPTOR; TRANSCRIPTION FACTOR RUNX2; TRANSCRIPTION FACTOR SIN3A;

ALZHEIMER DISEASE; AMYOTROPHIC LATERAL SCLEROSIS; CHROMATIN IMMUNOPRECIPITATION; CLINICAL TRIAL (TOPIC); DNA METHYLATION; FRAGILE X SYNDROME; FRIEDREICH ATAXIA; GENE EXPRESSION; GENE SILENCING; HISTONE ACETYLATION; HUMAN; HUNTINGTON CHOREA; NERVE DEGENERATION; NIEMANN PICK DISEASE; PARKINSON DISEASE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; REVIEW; SPINAL MUSCULAR ATROPHY; SPINOCEREBELLAR DEGENERATION;

EID: 84929878466     PISSN: None     EISSN: 23289503     Source Type: Journal    
DOI: 10.1002/acn3.147     Document Type: Review

References (304)

1. Gregoretti IV, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol 2004;338:17-31.
2. Dokmanovic M, Clarke C, Marks PA. Histone deacetylase inhibitors: overview and perspectives. Mol Cancer Res 2007;5:981-989.
3. Haberland M, Montgomery RL, Olson EN. The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 2009;10:32-42.
4. de Ruijter AJ, van Gennip AH, Caron HN, et al. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003;370(Pt 3):737-749.
5. Sauve AA, Wolberger C, Schramm VL, Boeke JD. The biochemistry of sirtuins. Annu Rev Biochem 2006;75:435-465.
6. Kazantsev AG, Thompson LM. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat Rev Drug Discovery 2008;7:854-868.
7. Waltregny D, De Leval L, Glenisson W, et al. Expression of histone deacetylase 8, a class I histone deacetylase, is restricted to cells showing smooth muscle differentiation in normal human tissues. Am J Pathol 2004;165:553-564.
8. Yang XJ, Seto E. Collaborative spirit of histone deacetylases in regulating chromatin structure and gene expression. Curr Opin Genet Dev 2003;13:143-153.
9. Karagianni P, Wong J. HDAC3: taking the SMRT-N-CoRrect road to repression. Oncogene 2007;26:5439-5449.
10. Polesskaya A, Duquet A, Naguibneva I, et al. CREB-binding protein/p300 activates MyoD by acetylation. J Biol Chem 2000;275:34359-34364.
11. Ito A, Kawaguchi Y, Lai CH, et al. MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation. EMBO J 2002;21:6236-6245.
12. Yao YL, Yang WM, Seto E. Regulation of transcription factor YY1 by acetylation and deacetylation. Mol Cell Biol 2001;21:5979-5991.
13. Kawai H, Yamada Y, Tatsuka M, et al. Down-regulation of nuclear factor kappaB is required for p53-dependent apoptosis in X-ray-irradiated mouse lymphoma cells and thymocytes. Cancer Res 1999;59:6038-6041.
14. Markham D, Munro S, Soloway J, et al. DNA-damage-responsive acetylation of pRb regulates binding to E2F-1. EMBO Rep 2006;7:192-198.
15. Marzio G, Wagener C, Gutierrez MI, et al. E2F family members are differentially regulated by reversible acetylation. J Biol Chem 2000;275:10887-10892.
16. 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.
17. Blanco-Garcia N, Asensio-Juan E, de la Cruz X, Martinez-Balbas MA. Autoacetylation regulates P/CAF nuclear localization. J Biol Chem 2009;284:1343-1352.
18. Thevenet L, Mejean C, Moniot B, et al. Regulation of human SRY subcellular distribution by its acetylation/deacetylation. EMBO J 2004;23:3336-3345.
19. Kramer OH, Knauer SK, Greiner G, et al. A phosphorylation-acetylation switch regulates STAT1 signaling. Genes Dev 2009;23:223-235.
20. Yuan ZL, Guan YJ, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005;307:269-273.
21. Chen L, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science 2001;293:1653-1657.
22. Guedes-Dias P, Oliveira JM. Lysine deacetylases and mitochondrial dynamics in neurodegeneration. Biochim Biophys Acta 2013;1832:1345-1359.
23. Verdel A, Curtet S, Brocard MP, et al. Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm. Curr Biol 2000;10:747-749.
24. Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubule-associated deacetylase. Nature 2002;417:455-458.
25. Kekatpure VD, Dannenberg AJ, Subbaramaiah K. HDAC6 modulates Hsp90 chaperone activity and regulates activation of aryl hydrocarbon receptor signaling. J Biol Chem 2009;284:7436-7445.
26. 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.
27. Li Y, Zhang X, Polakiewicz RD, et al. HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. J Biol Chem 2008;283:12686-12690.
28. Ellis JJ, Valencia TG, Zeng H, et al. CaM kinase IIdeltaC phosphorylation of 14-3-3beta in vascular smooth muscle cells: activation of class II HDAC repression. Mol Cell Biochem 2003;242:153-161.
29. Basile V, Mantovani R, Imbriano C. DNA damage promotes histone deacetylase 4 nuclear localization and repression of G2/M promoters, via p53 C-terminal lysines. J Biol Chem 2006;281:2347-2357.
30. Jeon EJ, Lee KY, Choi NS, et al. Bone morphogenetic protein-2 stimulates Runx2 acetylation. J Biol Chem 2006;281:16502-16511.
31. Glozak MA, Sengupta N, Zhang X, Seto E. Acetylation and deacetylation of non-histone proteins. Gene 2005;363:15-23.
32. Deardorff MA, Bando M, Nakato R, et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle. Nature 2012;489:313-317.
33. Jeong JW, Bae MK, Ahn MY, et al. Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation. Cell 2002;111:709-720.
34. Lai IL, Lin TP, Yao YL, et al. Histone deacetylase 10 relieves repression on the melanogenic program by maintaining the deacetylation status of repressors. J Biol Chem 2010;285:7187-7196.
35. Gupta MP, Samant SA, Smith SH, Shroff SG. HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity. J Biol Chem 2008;283:10135-10146.
36. Hageman J, Rujano MA, van Waarde MA, et al. A DNAJB chaperone subfamily with HDAC-dependent activities suppresses toxic protein aggregation. Mol Cell 2010;37:355-369.
37. Yuan Z, Peng L, Radhakrishnan R, Seto E. Histone deacetylase 9 (HDAC9) regulates the functions of the ATDC (TRIM29) protein. J Biol Chem 2010;285:39329-39338.
38. Blander G, Guarente L. The Sir2 family of protein deacetylases. Annu Rev Biochem 2004;73:417-435.
39. Frye RA. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem Biophys Res Commun 2000;273:793-798.
40. Michishita E, Park JY, Burneskis JM, et al. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol Biol Cell 2005;16:4623-4635.
41. Ramadori G, Lee CE, Bookout AL, et al. Brain SIRT1: anatomical distribution and regulation by energy availability. J Neurosci 2008;28:9989-9996.
42. Muth V, Nadaud S, Grummt I, Voit R. Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase I transcription. EMBO J 2001;20:1353-1362.
43. Bouras T, Fu M, Sauve AA, et al. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem 2005;280:10264-10276.
44. Cheng HL, Mostoslavsky R, Saito S, et al. Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-deficient mice. Proc Natl Acad Sci USA 2003;100:10794-10799.
45. Rodgers JT, Lerin C, Haas W, et al. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005;434:113-118.
46. Rothgiesser KM, Erener S, Waibel S, et al. SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci 2010;123(Pt 24):4251-4258.
47. North BJ, Marshall BL, Borra MT, et al. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 2003;11:437-444.
48. Schwer B, Bunkenborg J, Verdin RO, et al. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. Proc Natl Acad Sci USA 2006;103:10224-10229.
49. Schlicker C, Gertz M, Papatheodorou P, et al. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol 2008;382:790-801.
50. Ahn BH, Kim HS, Song S, et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 2008;105:14447-14452.
51. Sundaresan NR, Samant SA, Pillai VB, et al. SIRT3 is a stress-responsive deacetylase in cardiomyocytes that protects cells from stress-mediated cell death by deacetylation of Ku70. Mol Cell Biol 2008;28:6384-6401.
52. Yang H, Yang T, Baur JA, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell 2007;130:1095-1107.
53. Yang Y, Cimen H, Han MJ, et al. NAD+-dependent deacetylase SIRT3 regulates mitochondrial protein synthesis by deacetylation of the ribosomal protein MRPL10. J Biol Chem 2010;285:7417-7429.
54. Laurent G, German NJ, Saha AK, et al. SIRT4 coordinates the balance between lipid synthesis and catabolism by repressing malonyl CoA decarboxylase. Mol Cell 2013;50:686-698.
55. Nakagawa T, Lomb DJ, Haigis MC, Guarente L. SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 2009;137:560-570.
56. Kaidi A, Weinert BT, Choudhary C, Jackson SP. Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 2010;329:1348-1353.
57. Dominy JE Jr, Lee Y, Jedrychowski MP, et al. The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses hepatic gluconeogenesis. Mol Cell 2012;48:900-913.
58. Vakhrusheva O, Smolka C, Gajawada P, et al. Sirt7 increases stress resistance of cardiomyocytes and prevents apoptosis and inflammatory cardiomyopathy in mice. Circ Res 2008;102:703-710.
59. Gao L, Cueto MA, Asselbergs F, Atadja P. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem 2002;277:25748-25755.
60. Liu H, Hu Q, Kaufman A, et al. Developmental expression of histone deacetylase 11 in the murine brain. J Neurosci Res 2008;86:537-543.
61. Villagra A, Cheng F, Wang HW, et al. The histone deacetylase HDAC11 regulates the expression of interleukin 10 and immune tolerance. Nat Immunol 2009;10:92-100.
62. Cheung P, Allis CD, Sassone-Corsi P. Signaling to chromatin through histone modifications. Cell 2000;103:263-271.
63. Lill R. Function and biogenesis of iron-sulphur proteins. Nature 2009;460:831-838.
64. Martelli A, Napierala M, Puccio H. Understanding the genetic and molecular pathogenesis of Friedreich's ataxia through animal and cellular models. Dis Model Mech 2012;5:165-176.
65. Campuzano V, Montermini L, Molto MD, et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 1996;271:1423-1427.
66. Chutake YK, Lam C, Costello WN, et al. Epigenetic promoter silencing in Friedreich ataxia is dependent on repeat length. Ann Neurol 2014;76:522-528.
67. Tan G, Chen LS, Lonnerdal B, et al. Frataxin expression rescues mitochondrial dysfunctions in FRDA cells. Hum Mol Genet 2001;10:2099-2107.
68. Perdomini M, Belbellaa B, Monassier L, et al. Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia. Nat Med 2014;20:542-547.
69. Saveliev A, Everett C, Sharpe T, et al. DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing. Nature 2003;422:909-913.
70. Dion V, Wilson JH. Instability and chromatin structure of expanded trinucleotide repeats. Trends Genet 2009;25:288-297.
71. Herman D, Jenssen K, Burnett R, et al. Histone deacetylase inhibitors reverse gene silencing in Friedreich's ataxia. Nat Chem Biol 2006;2:551-558.
72. Greene E, Mahishi L, Entezam A, et al. Repeat-induced epigenetic changes in intron 1 of the frataxin gene and its consequences in Friedreich ataxia. Nucleic Acids Res 2007;35:3383-3390.
73. Punga T, Buhler M. Long intronic GAA repeats causing Friedreich ataxia impede transcription elongation. EMBO Mol Med 2010;2:120-129.
74. Kumari D, Biacsi RE, Usdin K. Repeat expansion affects both transcription initiation and elongation in Friedreich ataxia cells. J Biol Chem 2011;286:4209-4215.
75. Kim E, Napierala M, Dent SY. Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich's ataxia. Nucleic Acids Res 2011;39:8366-8377.
76. Peters AH, O'Carroll D, Scherthan H, et al. Loss of the Suv39h histone methyltransferases impairs mammalian heterochromatin and genome stability. Cell 2001;107:323-337.
77. De Biase I, Chutake YK, Rindler PM, Bidichandani SI. Epigenetic silencing in Friedreich ataxia is associated with depletion of CTCF (CCCTC-binding factor) and antisense transcription. PLoS One 2009;4:e7914.
78. Sarsero JP, Li L, Wardan H, et al. Upregulation of expression from the FRDA genomic locus for the therapy of Friedreich ataxia. J Gene Med 2003;5:72-81.
79. Rai M, Soragni E, Jenssen K, et al. HDAC inhibitors correct frataxin deficiency in a Friedreich ataxia mouse model. PLoS One 2008;3:e1958.
80. Sandi C, Pinto RM, Al-Mahdawi S, et al. Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model. Neurobiol Dis 2011;42:496-505.
81. Xu C, Soragni E, Chou CJ, et al. Chemical probes identify a role for histone deacetylase 3 in Friedreich's ataxia gene silencing. Chem Biol 2009;16:980-989.
82. Rai M, Soragni E, Chou CJ, et al. Two new pimelic diphenylamide HDAC inhibitors induce sustained frataxin upregulation in cells from Friedreich's ataxia patients and in a mouse model. PLoS One 2010;5:e8825.
83. Soragni E, Miao W, Iudicello M, et al. Epigenetic therapy for Friedreich ataxia. Ann Neurol 2014;76:489-508.
84. Chan PK, Torres R, Yandim C, et al. Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich's ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum Mol Genet 2013;22:2662-2675.
85. Libri V, Yandim C, Athanasopoulos S, et al. Epigenetic and neurological effects and safety of high-dose nicotinamide in patients with Friedreich's ataxia: an exploratory, open-label, dose-escalation study. Lancet 2014;384:504-513.
86. Antar LN, Dictenberg JB, Plociniak M, et al. Localization of FMRP-associated mRNA granules and requirement of microtubules for activity-dependent trafficking in hippocampal neurons. Genes Brain Behav 2005;4:350-359.
87. Pieretti M, Zhang FP, Fu YH, et al. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell 1991;66:817-822.
88. Coffee B, Zhang F, Warren ST, Reines D. Acetylated histones are associated with FMR1 in normal but not fragile X-syndrome cells. Nat Genet 1999;22:98-101.
89. Coffee B, Zhang F, Ceman S, et al. Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. Am J Hum Genet 2002;71:923-932.
90. Pietrobono R, Tabolacci E, Zalfa F, et al. Molecular dissection of the events leading to inactivation of the FMR1 gene. Hum Mol Genet 2005;14:267-277.
91. Tabolacci E, Pietrobono R, Moscato U, et al. Differential epigenetic modifications in the FMR1 gene of the fragile X syndrome after reactivating pharmacological treatments. Eur J Hum Genet 2005;13:641-648.
92. Eiges R, Urbach A, Malcov M, et al. Developmental study of fragile X syndrome using human embryonic stem cells derived from preimplantation genetically diagnosed embryos. Cell Stem Cell 2007;1:568-577.
93. Kumari D, Usdin K. The distribution of repressive histone modifications on silenced FMR1 alleles provides clues to the mechanism of gene silencing in fragile X syndrome. Hum Mol Genet 2010;19:4634-4642.
94. Kumari D, Usdin K. Interaction of the transcription factors USF1, USF2, and alpha -Pal/Nrf-1 with the FMR1 promoter. Implications for fragile X mental retardation syndrome. J Biol Chem 2001;276:4357-4364.
95. Naumann A, Hochstein N, Weber S, et al. A distinct DNA-methylation boundary in the 5′- upstream sequence of the FMR1 promoter binds nuclear proteins and is lost in fragile X syndrome. Am J Hum Genet 2009;85:606-616.
96. Chandler SP, Kansagra P, Hirst MC. Fragile X (CGG)n repeats induce a transcriptional repression in cis upon a linked promoter: evidence for a chromatin mediated effect. BMC Mol Biol 2003;4:3.
97. Chiurazzi P, Pomponi MG, Pietrobono R, et al. Synergistic effect of histone hyperacetylation and DNA demethylation in the reactivation of the FMR1 gene. Hum Mol Genet 1999;8:2317-2323.
98. Tabolacci E, De Pascalis I, Accadia M, et al. Modest reactivation of the mutant FMR1 gene by valproic acid is accompanied by histone modifications but not DNA demethylation. Pharmacogenet Genomics 2008;18:738-741.
99. Biacsi R, Kumari D, Usdin K. SIRT1 inhibition alleviates gene silencing in fragile X mental retardation syndrome. PLoS Genet 2008;4:e1000017.
100. Hagerman RJ, Leavitt BR, Farzin F, et al. Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. Am J Hum Genet 2004;74:1051-1056.
101. Tassone F, Hagerman RJ, Taylor AK, et al. Elevated levels of FMR1 mRNA in carrier males: a new mechanism of involvement in the fragile-X syndrome. Am J Hum Genet 2000;66:6-15.
102. Sofola OA, Jin P, Qin Y, et al. RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron 2007;55:565-571.
103. Aumiller V, Graebsch A, Kremmer E, et al. Drosophila Pur-alpha binds to trinucleotide-repeat containing cellular RNAs and translocates to the early oocyte. RNA Biol 2012;9:633-643.
104. Sellier C, Rau F, Liu Y, et al. Sam68 sequestration and partial loss of function are associated with splicing alterations in FXTAS patients. EMBO J 2010;29:1248-1261.
105. Sellier C, Freyermuth F, Tabet R, et al. Sequestration of DROSHA and DGCR8 by expanded CGG RNA repeats alters microRNA processing in fragile X-associated tremor/ataxia syndrome. Cell Rep 2013;3:869-880.
106. Todd PK, Oh SY, Krans A, et al. Histone deacetylases suppress CGG repeat-induced neurodegeneration via transcriptional silencing in models of fragile X tremor ataxia syndrome. PLoS Genet 2010;6:e1001240.
107. Mohseni J, Zabidi-Hussin ZA, Sasongko TH. Histone deacetylase inhibitors as potential treatment for spinal muscular atrophy. Genet Mol Biol 2013;36:299-307.
108. Edens BM, Ajroud-Driss S, Ma L, Ma YC. Molecular mechanisms and animal models of spinal muscular atrophy. Biochim Biophys Acta 2014; In press.
109. Monani UR, Sendtner M, Coovert DD, et al. The human centromeric survival motor neuron gene (SMN2) rescues embryonic lethality in Smn(-/-) mice and results in a mouse with spinal muscular atrophy. Hum Mol Genet 2000;9:333-339.
110. Arnold WD, Burghes AH. Spinal muscular atrophy: development and implementation of potential treatments. Ann Neurol 2013;74:348-362.
111. Kernochan LE, Russo ML, Woodling NS, et al. The role of histone acetylation in SMN gene expression. Hum Mol Genet 2005;14:1171-1182.
112. Andreassi C, Angelozzi C, Tiziano FD, et al. Phenylbutyrate increases SMN expression in vitro: relevance for treatment of spinal muscular atrophy. Eur J Hum Genet 2004;12:59-65.
113. Brichta L, Hofmann Y, Hahnen E, et al. Valproic acid increases the SMN2 protein level: a well-known drug as a potential therapy for spinal muscular atrophy. Hum Mol Genet 2003;12:2481-2489.
114. Chang JG, Hsieh-Li HM, Jong YJ, et al. Treatment of spinal muscular atrophy by sodium butyrate. Proc Natl Acad Sci USA 2001;98:9808-9813.
115. Avila AM, Burnett BG, Taye AA, et al. Trichostatin A increases SMN expression and survival in a mouse model of spinal muscular atrophy. J Clin Invest 2007;117:659-671.
116. Riessland M, Ackermann B, Forster A, et al. SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy. Hum Mol Genet 2010;19:1492-1506.
117. Weihl CC, Connolly AM, Pestronk A. Valproate may improve strength and function in patients with type III/IV spinal muscle atrophy. Neurology 2006;67:500-501.
118. Tsai LK, Yang CC, Hwu WL, Li H. Valproic acid treatment in six patients with spinal muscular atrophy. Eur J Neurol 2007;14:e8-e9.
119. Swoboda KJ, Scott CB, Reyna SP, et al. Phase II open label study of valproic acid in spinal muscular atrophy. PLoS One 2009;4:e5268.
120. Darbar IA, Plaggert PG, Resende MB, et al. Evaluation of muscle strength and motor abilities in children with type II and III spinal muscle atrophy treated with valproic acid. BMC Neurol 2011;11:36.
121. Swoboda KJ, Scott CB, Crawford TO, et al. SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy. PLoS One 2010;5:e12140.
122. Kissel JT, Scott CB, Reyna SP, et al. SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy. PLoS One 2011;6:e21296.
123. Kissel JT, Elsheikh B, King WM, et al. SMA valiant trial: a prospective, double-blind, placebo-controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy. Muscle Nerve 2014;49:187-192.
124. Vanier MT. [Niemann-Pick C disease: history, current research topics, biological and molecular diagnosis]. Arch Pediatr 2010;17(suppl 2):S41-S44.
125. Stern G. Niemann-Pick's and Gaucher's diseases. Parkinsonism Relat Disord 2014;20(suppl 1):S143-S146.
126. Blom TS, Linder MD, Snow K, et al. Defective endocytic trafficking of NPC1 and NPC2 underlying infantile Niemann-Pick type C disease. Hum Mol Genet 2003;12:257-272.
127. Liou HL, Dixit SS, Xu S, et al. NPC2, the protein deficient in Niemann-Pick C2 disease, consists of multiple glycoforms that bind a variety of sterols. J Biol Chem 2006;281:36710-36723.
128. Infante RE, Wang ML, Radhakrishnan A, et al. NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes. Proc Natl Acad Sci USA 2008;105:15287-15292.
129. Gelsthorpe ME, Baumann N, Millard E, et al. Niemann-Pick type C1 I1061T mutant encodes a functional protein that is selected for endoplasmic reticulum-associated degradation due to protein misfolding. J Biol Chem 2008;283:8229-8236.
130. Gevry NY, Lalli E, Sassone-Corsi P, Murphy BD. Regulation of niemann-pick c1 gene expression by the 3′5′-cyclic adenosine monophosphate pathway in steroidogenic cells. Mol Endocrinol 2003;17:704-715.
131. Pipalia NH, Cosner CC, Huang A, et al. Histone deacetylase inhibitor treatment dramatically reduces cholesterol accumulation in Niemann-Pick type C1 mutant human fibroblasts. Proc Natl Acad Sci USA 2011;108:5620-5625.
132. Cummings CJ, Zoghbi HY. Trinucleotide repeats: mechanisms and pathophysiology. Annu Rev Genomics Hum Genet 2000;1:281-328.
133. Nakamura K, Jeong SY, Uchihara T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 2001;10:1441-1448.
134. Opal P, Zoghbi HY. The role of chaperones in polyglutamine disease. Trends Mol Med 2002;8:232-236.
135. Opal P, Zoghbi HY. The hereditary ataxias. Principle and practice of medical genetics 2013;118:1-32.
136. 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 USA 2000;97:6763-6768.
137. McCampbell A, Taylor JP, Taye AA, et al. CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet 2000;9:2197-2202.
138. Sugars KL, Rubinsztein DC. Transcriptional abnormalities in Huntington disease. Trends Genet 2003;19:233-238.
139. Nucifora FC Jr, Sasaki M, Peters MF, et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 2001;291:2423-2428.
140. Palhan VB, Chen S, Peng GH, et al. Polyglutamine-expanded ataxin-7 inhibits STAGA histone acetyltransferase activity to produce retinal degeneration. Proc Natl Acad Sci USA 2005;102:8472-8477.
141. Li F, Macfarlan T, Pittman RN, Chakravarti D. Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities. J Biol Chem 2002;277:45004-45012.
142. Cvetanovic M, Kular RK, Opal P. LANP mediates neuritic pathology in Spinocerebellar ataxia type 1. Neurobiol Dis 2012;48:526-532.
143. Cvetanovic M, Patel JM, Marti HH, et al. Vascular endothelial growth factor ameliorates the ataxic phenotype in a mouse model of spinocerebellar ataxia type 1. Nat Med 2011;17:1445-1447.
144. Kular RK, Cvetanovic M, Siferd S, et al. Neuronal differentiation is regulated by leucine-rich acidic nuclear protein (LANP), a member of the inhibitor of histone acetyltransferase complex. J Biol Chem 2009;284:7783-7792.
145. Hogarth P, Lovrecic L, Krainc D. Sodium phenylbutyrate in Huntington's disease: a dose-finding study. Mov Disord 2007;22:1962-1964.
146. Ebbel EN, Leymarie N, Schiavo S, et al. Identification of phenylbutyrate-generated metabolites in Huntington disease patients using parallel liquid chromatography/electrochemical array/mass spectrometry and off-line tandem mass spectrometry. Anal Biochem 2010;399:152-161.
147. Venkatraman A, Hu YS, Didonna A, et al. The histone deacetylase HDAC3 is essential for Purkinje cell function, potentially complicating the use of HDAC inhibitors in SCA1. Hum Mol Genet 2014;23:3733-3745.
148. Moumne L, Campbell K, Howland D, et al. Genetic knock-down of HDAC3 does not modify disease-related phenotypes in a mouse model of Huntington's disease. PLoS One 2012;7:e31080.
149. Benn CL, Butler R, Mariner L, et al. Genetic knock-down of HDAC7 does not ameliorate disease pathogenesis in the R6/2 mouse model of Huntington's disease. PLoS One 2009;4:e5747.
150. Mielcarek M, Landles C, Weiss A, et al. HDAC4 reduction: a novel therapeutic strategy to target cytoplasmic huntingtin and ameliorate neurodegeneration. PLoS Biol 2013;11:e1001717.
151. Bobrowska A, Paganetti P, Matthias P, Bates GP. Hdac6 knock-out increases tubulin acetylation but does not modify disease progression in the R6/2 mouse model of Huntington's disease. PLoS One 2011;6:e20696.
152. Bobrowska A, Donmez G, Weiss A, et al. SIRT2 ablation has no effect on tubulin acetylation in brain, cholesterol biosynthesis or the progression of Huntington's disease phenotypes in vivo. PLoS One 2012;7:e34805.
153. Hammond JW, Cai D, Verhey KJ. Tubulin modifications and their cellular functions. Curr Opin Cell Biol 2008;20:71-76.
154. Chen S, Owens GC, Makarenkova H, Edelman DB. HDAC6 regulates mitochondrial transport in hippocampal neurons. PLoS One 2010;5:e10848.
155. Suzuki K, Koike T. Mammalian Sir2-related protein (SIRT) 2-mediated modulation of resistance to axonal degeneration in slow Wallerian degeneration mice: a crucial role of tubulin deacetylation. Neuroscience 2007;147:599-612.
156. Hempen B, Brion JP. Reduction of acetylated alpha-tubulin immunoreactivity in neurofibrillary tangle-bearing neurons in Alzheimer's disease. J Neuropathol Exp Neurol 1996;55:964-972.
157. 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.
158. Barisic N, Claeys KG, Sirotkovic-Skerlev M, et al. Charcot-Marie-Tooth disease: a clinico-genetic confrontation. Ann Hum Genet 2008;72(Pt 3):416-441.
159. Ostern R, Fagerheim T, Hjellnes H, et al. Diagnostic laboratory testing for Charcot Marie Tooth disease (CMT): the spectrum of gene defects in Norwegian patients with CMT and its implications for future genetic test strategies. BMC Med Genet 2013;14:94.
160. d'Ydewalle C, Benoy V, Van Den Bosch L. Charcot-Marie-Tooth disease: emerging mechanisms and therapies. Int J Biochem Cell Biol 2012;44:1299-1304.
161. d'Ydewalle C, Krishnan J, Chiheb DM, et al. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. Nat Med 2011;17:968-974.
162. Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis. Nat Rev Neurosci 2013;14:248-264.
163. Bilsland LG, Sahai E, Kelly G, et al. Deficits in axonal transport precede ALS symptoms in vivo. Proc Natl Acad Sci USA 2010;107:20523-20528.
164. Rosen DR. Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 1993;364:362.
165. Maruyama H, Morino H, Ito H, et al. Mutations of optineurin in amyotrophic lateral sclerosis. Nature 2010;465:223-226.
166. Deng HX, Chen W, Hong ST, et al. Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementia. Nature 2011;477:211-215.
167. 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.
168. Yoo YE, Ko CP. Treatment with trichostatin A initiated after disease onset delays disease progression and increases survival in a mouse model of amyotrophic lateral sclerosis. Exp Neurol 2011;231:147-159.
169. 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.
170. Cudkowicz ME, Andres PL, Macdonald SA, et al. Phase 2 study of sodium phenylbutyrate in ALS. Amyotroph Lateral Scler 2009;10:99-106.
171. Piepers S, Veldink JH, de Jong SW, et al. Randomized sequential trial of valproic acid in amyotrophic lateral sclerosis. Ann Neurol 2009;66:227-234.
172. Kim C, Choi H, Jung ES, et al. HDAC6 inhibitor blocks amyloid beta-induced impairment of mitochondrial transport in hippocampal neurons. PLoS One 2012;7:e42983.
173. Selenica ML, Benner L, Housley SB, et al. Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition. Alzheimers Res Ther 2014;6:12.
174. Xiong Y, Zhao K, Wu J, et al. HDAC6 mutations rescue human tau-induced microtubule defects in Drosophila. Proc Natl Acad Sci USA 2013;110:4604-4609.
175. Govindarajan N, Rao P, Burkhardt S, et al. Reducing HDAC6 ameliorates cognitive deficits in a mouse model for Alzheimer's disease. EMBO Mol Med 2013;5:52-63.
176. Cook C, Carlomagno Y, Gendron TF, et al. Acetylation of the KXGS motifs in tau is a critical determinant in modulation of tau aggregation and clearance. Hum Mol Genet 2014;23:104-116.
177. 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.
178. Inden M, Kitamura Y, Takeuchi H, et al. Neurodegeneration of mouse nigrostriatal dopaminergic system induced by repeated oral administration of rotenone is prevented by 4-phenylbutyrate, a chemical chaperone. J Neurochem 2007;101:1491-1504.
179. Gardian G, Yang L, Cleren C, et al. Neuroprotective effects of phenylbutyrate against MPTP neurotoxicity. Neuromolecular Med 2004;5:235-241.
180. Ono K, Ikemoto M, Kawarabayashi T, et al. A chemical chaperone, sodium 4-phenylbutyric acid, attenuates the pathogenic potency in human alpha-synuclein A30P + A53T transgenic mice. Parkinsonism Relat Disord 2009;15:649-654.
181. Monti B, Mercatelli D, Contestabile A. Valproic acid neuroprotection in 6-OHDA lesioned rat, a model for Parkinson's disease. HOAJ Biol 2012;1:1-4.
182. Kawaguchi Y, Kovacs JJ, McLaurin A, et al. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003;115:727-738.
183. Lee JY, Koga H, Kawaguchi Y, et al. HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy. EMBO J 2010;29:969-980.
184. Kovacs JJ, Murphy PJ, Gaillard S, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 2005;18:601-607.
185. Pandey UB, Nie Z, Batlevi Y, et al. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 2007;447:859-863.
186. Roth M, Chen WY. Sorting out functions of sirtuins in cancer. Oncogene 2014;33:1609-1620.
187. Morris MJ, Mahgoub M, Na ES, et al. Loss of histone deacetylase 2 improves working memory and accelerates extinction learning. J Neurosci 2013;33:6401-6411.
188. 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.
189. 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.
190. Sando R III, Gounko N, Pieraut S, et al. HDAC4 governs a transcriptional program essential for synaptic plasticity and memory. Cell 2012;151:821-834.
191. Renthal W, Maze I, Krishnan V, et al. Histone deacetylase 5 epigenetically controls behavioral adaptations to chronic emotional stimuli. Neuron 2007;56:517-529.
192. Espallergues J, Teegarden SL, Veerakumar A, et al. HDAC6 regulates glucocorticoid receptor signaling in serotonin pathways with critical impact on stress resilience. J Neurosci 2012;32:4400-4416.
193. Michan S, Li Y, Chou MM, et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. J Neurosci 2010;30:9695-9707.
194. Bellet MM, Nakahata Y, Boudjelal M, et al. Pharmacological modulation of circadian rhythms by synthetic activators of the deacetylase SIRT1. Proc Natl Acad Sci USA 2013;110:3333-3338.
195. Herskovits AZ, Guarente L. SIRT1 in neurodevelopment and brain senescence. Neuron 2014;81:471-483.
196. Bardai FH, Price V, Zaayman M, et al. Histone deacetylase-1 (HDAC1) is a molecular switch between neuronal survival and death. J Biol Chem 2012;287:35444-35453.
197. Bardai FH, D'Mello SR. Selective toxicity by HDAC3 in neurons: regulation by Akt and GSK3beta. J Neurosci 2011;31:1746-1751.
198. Linseman DA, Bartley CM, Le SS, et al. Inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca(2 + )//calmodulin-dependent kinase II promotes depolarization-mediated cerebellar granule neuron survival. J Biol Chem 2003;278:41472-41481.
199. Majdzadeh N, Wang L, Morrison BE, et al. HDAC4 inhibits cell-cycle progression and protects neurons from cell death. Dev Neurobiol 2008;68:1076-1092.
200. Morrison BE, Majdzadeh N, Zhang X, et al. Neuroprotection by histone deacetylase-related protein. Mol Cell Biol 2006;26:3550-3564.
201. Pfister JA, Ma C, Morrison BE, D'Mello SR. Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity. PLoS One 2008;3:e4090.
202. Broide RS, Redwine JM, Aftahi N, et al. Distribution of histone deacetylases 1-11 in the rat brain. J Mol Neurosci 2007;31:47-58.
203. Donmez G. The neurobiology of sirtuins and their role in neurodegeneration. Trends Pharmacol Sci 2012;33:494-501.
204. Zhang F, Wang S, Gan L, et al. Protective effects and mechanisms of sirtuins in the nervous system. Prog Neurobiol 2011;95:373-395.
205. Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 2007;25:84-90.
206. Butler KV, Kalin J, Brochier C, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc 2010;132:10842-10846.
207. Glaser KB. HDAC inhibitors: clinical update and mechanism-based potential. Biochem Pharmacol 2007;74:659-671.
208. Haggarty SJ, Koeller KM, Wong JC, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc Natl Acad Sci USA 2003;100:4389-4394.
209. Furumai R, Matsuyama A, Kobashi N, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002;62:4916-4921.
210. Xu WS, Parmigiani RB, Marks PA. Histone deacetylase inhibitors: molecular mechanisms of action. Oncogene 2007;26:5541-5552.
211. 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;101:15064-15069.
212. Thomas EA, Coppola G, Desplats PA, et al. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice. Proc Natl Acad Sci USA 2008;105:15564-15569.
213. Sauve AA, Schramm VL. Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry 2003;42:9249-9256.
214. Bedalov A, Gatbonton T, Irvine WP, et al. Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci USA 2001;98:15113-15118.
215. Grozinger CM, Chao ED, Blackwell HE, et al. Identification of a class of small molecule inhibitors of the sirtuin family of NAD-dependent deacetylases by phenotypic screening. J Biol Chem 2001;276:38837-38843.
216. Taylor DM, Balabadra U, Xiang Z, et al. A brain-permeable small molecule reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase. ACS Chem Biol 2011;6:540-546.
217. Friden-Saxin M, Seifert T, Landergren MR, et al. Synthesis and evaluation of substituted chroman-4-one and chromone derivatives as sirtuin 2-selective inhibitors. J Med Chem 2012;55:7104-7113.
218. Li SH, Cheng AL, Zhou H, et al. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol 2002;22:1277-1287.
219. Boutell JM, Thomas P, Neal JW, et al. Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. Hum Mol Genet 1999;8:1647-1655.
220. Takano H, Gusella JF. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci 2002;3:15.
221. Dunah AW, Jeong H, Griffin A, et al. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002;296:2238-2243.
222. McFarland KN, Huizenga MN, Darnell SB, et al. MeCP2: a novel Huntingtin interactor. Hum Mol Genet 2014;23:1036-1044.
223. Steffan JS, Bodai L, Pallos J, et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001;413:739-743.
224. Tsuda H, Jafar-Nejad H, Patel AJ, et al. The AXH domain of ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Cell 2005;122:633-644.
225. Lam YC, Bowman AB, Jafar-Nejad P, et al. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell 2006;127:1335-1347.
226. Mizutani A, Wang L, Rajan H, et al. Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1. EMBO J 2005;24:3339-3351.
227. Serra HG, Duvick L, Zu T, et al. RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell 2006;127:697-708.
228. Matilla A, Koshy BT, Cummings CJ, et al. The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1. Nature 1997;389:974-978.
229. Davidson JD, Riley B, Burright EN, et al. Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein. Hum Mol Genet 2000;9:2305-2312.
230. Shibata H, Huynh DP, Pulst SM. A novel protein with RNA-binding motifs interacts with ataxin-2. Hum Mol Genet 2000;9:1303-1313.
231. Elden AC, Kim HJ, Hart MP, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature 2010;466:1069-1075.
232. Nonhoff U, Ralser M, Welzel F, et al. Ataxin-2 interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules. Mol Biol Cell 2007;18:1385-1396.
233. Damrath E, Heck MV, Gispert S, et al. ATXN2-CAG42 sequesters PABPC1 into insolubility and induces FBXW8 in cerebellum of old ataxic knock-in mice. PLoS Genet 2012;8:e1002920.
234. Araujo J, Breuer P, Dieringer S, et al. FOXO4-dependent upregulation of superoxide dismutase-2 in response to oxidative stress is impaired in spinocerebellar ataxia type 3. Hum Mol Genet 2011;20:2928-2941.
235. Doss-Pepe EW, Stenroos ES, Johnson WG, Madura K. Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis. Mol Cell Biol 2003;23:6469-6483.
236. Shimohata T, Nakajima T, Yamada M, et al. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nat Genet 2000;26:29-36.
237. Evert BO, Araujo J, Vieira-Saecker AM, et al. Ataxin-3 represses transcription via chromatin binding, interaction with histone deacetylase 3, and histone deacetylation. J Neurosci 2006;26:11474-11486.
238. La Spada AR, Fu YH, Sopher BL, et al. Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7. Neuron 2001;31:913-927.
239. Lebre AS, Jamot L, Takahashi J, et al. Ataxin-7 interacts with a Cbl-associated protein that it recruits into neuronal intranuclear inclusions. Hum Mol Genet 2001;10:1201-1213.
240. Takahashi M, Obayashi M, Ishiguro T, et al. Cytoplasmic location of alpha1A voltage-gated calcium channel C-terminal fragment (Cav2.1-CTF) aggregate is sufficient to cause cell death. PLoS One 2013;8:e50121.
241. Lee LC, Chen CM, Wang HC, et al. Role of the CCAAT-binding protein NFY in SCA17 pathogenesis. PLoS One 2012;7:e35302.
242. Klejman MP, Zhao X, van Schaik FM, et al. Mutational analysis of BTAF1-TBP interaction: BTAF1 can rescue DNA-binding defective TBP mutants. Nucleic Acids Res 2005;33:5426-5436.
243. Alen P, Claessens F, Verhoeven G, et al. The androgen receptor amino-terminal domain plays a key role in p160 coactivator-stimulated gene transcription. Mol Cell Biol 1999;19:6085-6097.
244. Fu M, Wang C, Reutens AT, et al. p300 and p300/cAMP-response element-binding protein-associated factor acetylate the androgen receptor at sites governing hormone-dependent transactivation. J Biol Chem 2000;275:20853-20860.
245. Masiello D, Chen SY, Xu Y, et al. Recruitment of beta-catenin by wild-type or mutant androgen receptors correlates with ligand-stimulated growth of prostate cancer cells. Mol Endocrinol 2004;18:2388-2401.
246. McEwan IJ, Gustafsson J. Interaction of the human androgen receptor transactivation function with the general transcription factor TFIIF. Proc Natl Acad Sci USA 1997;94:8485-8490.
247. Wang L, Charroux B, Kerridge S, Tsai CC. Atrophin recruits HDAC1/2 and G9a to modify histone H3K9 and to determine cell fates. EMBO Rep 2008;9:555-562.
248. Wood JD, Yuan J, Margolis RL, et al. Atrophin-1, the DRPLA gene product, interacts with two families of WW domain-containing proteins. Mol Cell Neurosci 1998;11:149-160.
249. Wood JD, Nucifora FC Jr, Duan K, et al. Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription. J Cell Biol 2000;150:939-948.
250. 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;100:2041-2046.
251. Bates EA, Victor M, Jones AK, et al. Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity. J Neurosci 2006;26:2830-2838.
252. Sadri-Vakili G, Bouzou B, Benn CL, et al. Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models. Hum Mol Genet 2007;16:1293-1306.
253. Pallos J, Bodai L, Lukacsovich T, et al. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease. Hum Mol Genet 2008;17:3767-3775.
254. Zadori D, Geisz A, Vamos E, et al. Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington's disease. Pharmacol Biochem Behav 2009;94:148-153.
255. Hathorn T, Snyder-Keller A, Messer A. Nicotinamide improves motor deficits and upregulates PGC-1alpha and BDNF gene expression in a mouse model of Huntington's disease. Neurobiol Dis 2011;41:43-50.
256. 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.
257. 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.
258. Jia H, Pallos J, Jacques V, et al. Histone deacetylase (HDAC) inhibitors targeting HDAC3 and HDAC1 ameliorate polyglutamine-elicited phenotypes in model systems of Huntington's disease. Neurobiol Dis 2012;46:351-361.
259. Mielcarek M, Benn CL, Franklin SA, et al. SAHA decreases HDAC 2 and 4 levels in vivo and improves molecular phenotypes in the R6/2 mouse model of Huntington's disease. PLoS One 2011;6:e27746.
260. Jia H, Kast RJ, Steffan JS, Thomas EA. Selective histone deacetylase (HDAC) inhibition imparts beneficial effects in Huntington's disease mice: implications for the ubiquitin-proteasomal and autophagy systems. Hum Mol Genet 2012;21:5280-5293.
261. Chiu CT, Liu G, Leeds P, Chuang DM. Combined treatment with the mood stabilizers lithium and valproate produces multiple beneficial effects in transgenic mouse models of Huntington's disease. Neuropsychopharmacology 2011;36:2406-2421.
262. Luthi-Carter R, Taylor DM, Pallos J, et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc Natl Acad Sci USA 2010;107:7927-7932.
263. Chopra V, Quinti L, Kim J, et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models. Cell Rep 2012;2:1492-1497.
264. Chou AH, Chen SY, Yeh TH, et al. HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol Dis 2011;41:481-488.
265. Yi J, Zhang L, Tang B, et al. Sodium valproate alleviates neurodegeneration in SCA3/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4. PLoS One 2013;8:e54792.
266. Chou AH, Chen YL, Hu SH, et al. Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation. Brain Res 2014;1583:220-229.
267. 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.
268. Ying M, Xu R, Wu X, et al. Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA. J Biol Chem 2006;281:12580-12586.
269. Montgomery RL, Hsieh J, Barbosa AC, et al. Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development. Proc Natl Acad Sci USA 2009;106:7876-7881.
270. 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.
271. Jacob C, Lotscher P, Engler S, et al. HDAC1 and HDAC2 control the specification of neural crest cells into peripheral glia. J Neurosci 2014;34:6112-6122.
272. Chen B, Cepko CL. HDAC4 regulates neuronal survival in normal and diseased retinas. Science 2009;323:256-259.
273. Cho Y, Sloutsky R, Naegle KM, Cavalli V. Injury-induced HDAC5 nuclear export is essential for axon regeneration. Cell 2013;155:894-908.
274. Tapia M, Wandosell F, Garrido JJ. Impaired function of HDAC6 slows down axonal growth and interferes with axon initial segment development. PLoS One 2010;5:e12908.
275. Ageta-Ishihara N, Miyata T, Ohshima C, et al. Septins promote dendrite and axon development by negatively regulating microtubule stability via HDAC6-mediated deacetylation. Nat Commun 2013;4:2532.
276. Sugo N, Oshiro H, Takemura M, et al. Nucleocytoplasmic translocation of HDAC9 regulates gene expression and dendritic growth in developing cortical neurons. Eur J Neurosci 2010;31:1521-1532.
277. Li XH, Chen C, Tu Y, et al. Sirt1 promotes axonogenesis by deacetylation of Akt and inactivation of GSK3. Mol Neurobiol 2013;48:490-499.
278. Sugino T, Maruyama M, Tanno M, et al. Protein deacetylase SIRT1 in the cytoplasm promotes nerve growth factor-induced neurite outgrowth in PC12 cells. FEBS Lett 2010;584:2821-2826.
279. Codocedo JF, Allard C, Godoy JA, et al. SIRT1 regulates dendritic development in hippocampal neurons. PLoS One 2012;7:e47073.
280. Hisahara S, Chiba S, Matsumoto H, et al. Histone deacetylase SIRT1 modulates neuronal differentiation by its nuclear translocation. Proc Natl Acad Sci USA 2008;105:15599-15604.
281. Prozorovski T, Schulze-Topphoff U, Glumm R, et al. Sirt1 contributes critically to the redox-dependent fate of neural progenitors. Nat Cell Biol 2008;10:385-394.
282. Beirowski B, Gustin J, Armour SM, et al. Sir-two-homolog 2 (Sirt2) modulates peripheral myelination through polarity protein Par-3/atypical protein kinase C (aPKC) signaling. Proc Natl Acad Sci USA 2011;108:E952-E961.
283. Bahari-Javan S, Maddalena A, Kerimoglu C, et al. HDAC1 regulates fear extinction in mice. J Neurosci 2012;32:5062-5073.
284. Guan JS, Haggarty SJ, Giacometti E, et al. HDAC2 negatively regulates memory formation and synaptic plasticity. Nature 2009;459:55-60.
285. Jiang Y, Hsieh J. HDAC3 controls gap 2/mitosis progression in adult neural stem/progenitor cells by regulating CDK1 levels. Proc Natl Acad Sci USA 2014;111:13541-13546.
286. Rogge GA, Singh H, Dang R, Wood MA. HDAC3 is a negative regulator of cocaine-context-associated memory formation. J Neurosci 2013;33:6623-6632.
287. Kumar A, Choi KH, Renthal W, et al. Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum. Neuron 2005;48:303-314.
288. Fukada M, Hanai A, Nakayama A, et al. Loss of deacetylation activity of Hdac6 affects emotional behavior in mice. PLoS One 2012;7:e30924.
289. Lu M, Sarruf DA, Li P, et al. Neuronal Sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues. J Biol Chem 2013;288:10722-10735.
290. Wu D, Qiu Y, Gao X, et al. Overexpression of SIRT1 in mouse forebrain impairs lipid/glucose metabolism and motor function. PLoS One 2011;6:e21759.
291. Li Y, Xu W, McBurney MW, Longo VD. SirT1 inhibition reduces IGF-I/IRS-2/Ras/ERK1/2 signaling and protects neurons. Cell Metab 2008;8:38-48.
292. Saharan S, Jhaveri DJ, Bartlett PF. SIRT1 regulates the neurogenic potential of neural precursors in the adult subventricular zone and hippocampus. J Neurosci Res 2013;91:642-659.
293. Ramadori G, Fujikawa T, Fukuda M, et al. SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. Cell Metab 2010;12:78-87.
294. Sasaki T, Kikuchi O, Shimpuku M, et al. Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. Diabetologia 2014;57:819-831.
295. Kakefuda K, Fujita Y, Oyagi A, et al. Sirtuin 1 overexpression mice show a reference memory deficit, but not neuroprotection. Biochem Biophys Res Commun 2009;387:784-788.
296. Rafalski VA, Ho PP, Brett JO, et al. Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain. Nat Cell Biol 2013;15:614-624.
297. Chang HC, Guarente L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 2013;153:1448-1460.
298. Cohen DE, Supinski AM, Bonkowski MS, et al. Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction. Genes Dev 2009;23:2812-2817.
299. Satoh A, Brace CS, Ben-Josef G, et al. SIRT1 promotes the central adaptive response to diet restriction through activation of the dorsomedial and lateral nuclei of the hypothalamus. J Neurosci 2010;30:10220-10232.
300. Gao J, Wang WY, Mao YW, et al. A novel pathway regulates memory and plasticity via SIRT1 and miR-134. Nature 2010;466:1105-1109.
301. Ferguson D, Koo JW, Feng J, et al. Essential role of SIRT1 signaling in the nucleus accumbens in cocaine and morphine action. J Neurosci 2013;33:16088-16098.
302. Shih J, Mason A, Liu L, et al. Loss of SIRT4 decreases GLT-1-dependent glutamate uptake and increases sensitivity to kainic acid. J Neurochem 2014;131:573-581.
303. Schwer B, Schumacher B, Lombard DB, et al. Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc Natl Acad Sci USA 2010;107:21790-21794.
304. Silberman DM, Ross K, Sande PH, et al. SIRT6 is required for normal retinal function. PLoS One 2014;9:e98831.