 |
||||
|
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, October 15, 2003, 23(28):9418-9427
Previous Article | Next Article
Cellular/Molecular
Histone Deacetylase Inhibition by Sodium Butyrate Chemotherapy Ameliorates the Neurodegenerative Phenotype in Huntington's Disease Mice
Robert J. Ferrante,1,2 James K. Kubilus,1,2 Junghee Lee,1,2 Hoon Ryu,1,2 Ayshe Beesen,5,6 Birgit Zucker,5,6 Karen Smith,1,2 Neil W. Kowall,1,2 Rajiv R. Ratan,3,4 Ruth Luthi-Carter,5,6 andSteven M. Hersch5,6 1Geriatric Research Education and Clinical Center, Bedford Veterans Affairs Medical Center, Bedford, Massachusetts 01730, 2Departments of Neurology, Pathology, and Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118, 3Department of Neurology and Program in Neuroscience, Harvard Medical School, 4Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, 5Neurology Service, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and 6Center for Aging, Genetics, and Neurodegeneration, Massachusetts General Hospital, Charlestown, Massachusetts 02129
The precise cause of neuronal death in Huntington's disease (HD) is unknown. Although no single specific protein-protein interaction of mutant huntingtin has emerged as the pathologic trigger, transcriptional dysfunction may contribute to the neurodegeneration observed in HD. Pharmacological treatment using the histone deacetylase inhibitor sodium butyrate to modulate transcription significantly extended survival in a dose-dependent manner, improved body weight and motor performance, and delayed the neuropathological sequelae in the R6/2 transgenic mouse model of HD. Sodium butyrate also increased histone and Specificity protein-1 acetylation and protected against 3-nitropropionic acid neurotoxicity. Microarray analysis showed increased expression of
- and
-globins and MAP kinase phosphatase-1 in sodium butyrate-treated R6/2 mice, indicative of improved oxidative phosphorylation and transcriptional regulation. These findings strengthen the hypothesis that transcriptional dysfunction plays a role in the pathogenesis of HD and suggest that therapies aimed at modulating transcription may target early pathological events and provide clinical benefits to HD patients.
Key words: Huntington's disease; therapy; sodium butyrate; histones; transcription; microarray analysis; neuroprotection; R6/2 transgenic mice
Received May 24, 2003; revised August 19, 2003; accepted August 20, 2003.
This article has been cited by other articles:
T. Uo, T. D. Veenstra, and R. S. Morrison
Histone Deacetylase Inhibitors Prevent p53-Dependent and p53-Independent Bax-Mediated Neuronal Apoptosis through Two Distinct Mechanisms
J. Neurosci., March 4, 2009; 29(9): 2824 - 2832.
[Abstract] [Full Text] [PDF]
J. Pallos, L. Bodai, T. Lukacsovich, J. M. Purcell, J. S. Steffan, L. M. Thompson, and J. L. Marsh
Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease
Hum. Mol. Genet., December 1, 2008; 17(23): 3767 - 3775.
[Abstract] [Full Text] [PDF]
K. N. Green, J. S. Steffan, H. Martinez-Coria, X. Sun, S. S. Schreiber, L. M. Thompson, and F. M. LaFerla
Nicotinamide Restores Cognition in Alzheimer's Disease Transgenic Mice via a Mechanism Involving Sirtuin Inhibition and Selective Reduction of Thr231-Phosphotau
J. Neurosci., November 5, 2008; 28(45): 11500 - 11510.
[Abstract] [Full Text] [PDF]
E. A. Thomas, G. Coppola, P. A. Desplats, B. Tang, E. Soragni, R. Burnett, F. Gao, K. M. Fitzgerald, J. F. Borok, D. Herman, et al.
The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice
PNAS, October 7, 2008; 105(40): 15564 - 15569.
[Abstract] [Full Text] [PDF]
M. B. Ramocki, L. Chapieski, R. O. McDonald, F. Fernandez, and A. D. Malphrus
Spinocerebellar Ataxia Type 2 Presenting With Cognitive Regression in Childhood
J Child Neurol, September 1, 2008; 23(9): 999 - 1001.
[Abstract] [PDF]
J. Shao, W. J. Welch, N. A. DiProspero, and M. I. Diamond
Phosphorylation of Profilin by ROCK1 Regulates Polyglutamine Aggregation
Mol. Cell. Biol., September 1, 2008; 28(17): 5196 - 5208.
[Abstract] [Full Text] [PDF]
S. C. Pandey, R. Ugale, H. Zhang, L. Tang, and A. Prakash
Brain Chromatin Remodeling: A Novel Mechanism of Alcoholism
J. Neurosci., April 2, 2008; 28(14): 3729 - 3737.
[Abstract] [Full Text] [PDF]
E. Roze, S. Betuing, C. Deyts, E. Marcon, K. Brami-Cherrier, C. Pages, S. Humbert, K. Merienne, and J. Caboche
Mitogen- and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death
FASEB J, April 1, 2008; 22(4): 1083 - 1093.
[Abstract] [Full Text] [PDF]
F. Giorgini, T. Moller, W. Kwan, D. Zwilling, J. L. Wacker, S. Hong, L.-C. L. Tsai, C. S. Cheah, R. Schwarcz, P. Guidetti, et al.
Histone Deacetylase Inhibition Modulates Kynurenine Pathway Activation in Yeast, Microglia, and Mice Expressing a Mutant Huntingtin Fragment
J. Biol. Chem., March 21, 2008; 283(12): 7390 - 7400.
[Abstract] [Full Text] [PDF]
E. C. Stack, A. Dedeoglu, K. M. Smith, K. Cormier, J. K. Kubilus, M. Bogdanov, W. R. Matson, L. Yang, B. G. Jenkins, R. Luthi-Carter, et al.
Neuroprotective Effects of Synaptic Modulation in Huntington's Disease R6/2 Mice
J. Neurosci., November 21, 2007; 27(47): 12908 - 12915.
[Abstract] [Full Text] [PDF]
W. B. Chwang, J. S. Arthur, A. Schumacher, and J. D. Sweatt
The Nuclear Kinase Mitogen- and Stress-Activated Protein Kinase 1 Regulates Hippocampal Chromatin Remodeling in Memory Formation
J. Neurosci., November 14, 2007; 27(46): 12732 - 12742.
[Abstract] [Full Text] [PDF]
V. Chopra, J. H. Fox, G. Lieberman, K. Dorsey, W. Matson, P. Waldmeier, D. E. Housman, A. Kazantsev, A. B. Young, and S. Hersch
A small-molecule therapeutic lead for Huntington's disease: Preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse
PNAS, October 16, 2007; 104(42): 16685 - 16689.
[Abstract] [Full Text] [PDF]
J. Shao and M. I. Diamond
Polyglutamine diseases: emerging concepts in pathogenesis and therapy
Hum. Mol. Genet., October 15, 2007; 16(R2): R115 - R123.
[Abstract] [Full Text] [PDF]
T. A. Bolger, X. Zhao, T. J. Cohen, C.-C. Tsai, and T.-P. Yao
The Neurodegenerative Disease Protein Ataxin-1 Antagonizes the Neuronal Survival Function of Myocyte Enhancer Factor-2
J. Biol. Chem., October 5, 2007; 282(40): 29186 - 29192.
[Abstract] [Full Text] [PDF]
H. Varma, R. Cheng, C. Voisine, A. C. Hart, and B. R. Stockwell
Inhibitors of metabolism rescue cell death in Huntington's disease models
PNAS, September 4, 2007; 104(36): 14525 - 14530.
[Abstract] [Full Text] [PDF]
A. Kuhn, D. R. Goldstein, A. Hodges, A. D. Strand, T. Sengstag, C. Kooperberg, K. Becanovic, M. A. Pouladi, K. Sathasivam, J.-H. J. Cha, et al.
Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage
Hum. Mol. Genet., August 1, 2007; 16(15): 1845 - 1861.
[Abstract] [Full Text] [PDF]
D. M. Neumann, P. S. Bhattacharjee, and J. M. Hill
Sodium Butyrate: a Chemical Inducer of In Vivo Reactivation of Herpes Simplex Virus Type 1 in the Ocular Mouse Model
J. Virol., June 1, 2007; 81(11): 6106 - 6110.
[Abstract] [Full Text] [PDF]
H. J. Kim, M. Rowe, M. Ren, J.-S. Hong, P.-S. Chen, and D.-M. Chuang
Histone Deacetylase Inhibitors Exhibit Anti-Inflammatory and Neuroprotective Effects in a Rat Permanent Ischemic Model of Stroke: Multiple Mechanisms of Action
J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 892 - 901.
[Abstract] [Full Text] [PDF]
G. Sadri-Vakili, B. Bouzou, C. L. Benn, M.-O. Kim, P. Chawla, R. P. Overland, K. E. Glajch, E. Xia, Z. Qiu, S. M. Hersch, et al.
Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models
Hum. Mol. Genet., June 1, 2007; 16(11): 1293 - 1306.
[Abstract] [Full Text] [PDF]
C. Rouaux, I. Panteleeva, F. Rene, J.-L. Gonzalez de Aguilar, A. Echaniz-Laguna, L. Dupuis, Y. Menger, A.-L. Boutillier, and J.-P. Loeffler
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., May 23, 2007; 27(21): 5535 - 5545.
[Abstract] [Full Text] [PDF]
E. C. Stack, S. J. Del Signore, R. Luthi-Carter, B. Y. Soh, D. R. Goldstein, S. Matson, S. Goodrich, A. L. Markey, K. Cormier, S. W. Hagerty, et al.
Modulation of nucleosome dynamics in Huntington's disease
Hum. Mol. Genet., May 15, 2007; 16(10): 1164 - 1175.
[Abstract] [Full Text] [PDF]
M.-C. Chiang, C.-G. Juo, H.-H. Chang, H.-M. Chen, E. C. Yi, and Y. Chern
Systematic Uncovering of Multiple Pathways Underlying the Pathology of Huntington Disease by an Acid-cleavable Isotope-coded Affinity Tag Approach
Mol. Cell. Proteomics, May 1, 2007; 6(5): 781 - 797.
[Abstract] [Full Text] [PDF]
M. Latouche, C. Lasbleiz, E. Martin, V. Monnier, T. Debeir, A. Mouatt-Prigent, M.-P. Muriel, L. Morel, M. Ruberg, A. Brice, et al.
A Conditional Pan-Neuronal Drosophila Model of Spinocerebellar Ataxia 7 with a Reversible Adult Phenotype Suitable for Identifying Modifier Genes
J. Neurosci., March 7, 2007; 27(10): 2483 - 2492.
[Abstract] [Full Text] [PDF]
H. Ryu, J. Lee, S. W. Hagerty, B. Y. Soh, S. E. McAlpin, K. A. Cormier, K. M. Smith, and R. J. Ferrante
ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease
PNAS, December 12, 2006; 103(50): 19176 - 19181.
[Abstract] [Full Text] [PDF]
G. Faraco, T. Pancani, L. Formentini, P. Mascagni, G. Fossati, F. Leoni, F. Moroni, and A. Chiarugi
Pharmacological Inhibition of Histone Deacetylases by Suberoylanilide Hydroxamic Acid Specifically Alters Gene Expression and Reduces Ischemic Injury in the Mouse Brain
Mol. Pharmacol., December 1, 2006; 70(6): 1876 - 1884.
[Abstract] [Full Text] [PDF]
J. M. A. Oliveira, S. Chen, S. Almeida, R. Riley, J. Goncalves, C. R. Oliveira, M. R. Hayden, D. G. Nicholls, L. M. Ellerby, and A. C. Rego
Mitochondrial-Dependent Ca2+ Handling in Huntington's Disease Striatal Cells: Effect of Histone Deacetylase Inhibitors
J. Neurosci., October 25, 2006; 26(43): 11174 - 11186.
[Abstract] [Full Text] [PDF]
E. Kontopoulos, J. D. Parvin, and M. B. Feany
{alpha}-synuclein acts in the nucleus to inhibit histone acetylation and promote neurotoxicity
Hum. Mol. Genet., October 15, 2006; 15(20): 3012 - 3023.
[Abstract] [Full Text] [PDF]
S. Finkbeiner, A. Maria Cuervo, R. I. Morimoto, and P. J. Muchowski
Disease-Modifying Pathways in Neurodegeneration
J. Neurosci., October 11, 2006; 26(41): 10349 - 10357.
[Full Text] [PDF]
B. E. Riley and H. T Orr
Polyglutamine neurodegenerative diseases and regulation of transcription: assembling the puzzle.
Genes & Dev., August 15, 2006; 20(16): 2183 - 2192.
[Abstract] [Full Text] [PDF]
N. Zhong, C. Y. Kim, P. Rizzu, C. Geula, D. R. Porter, E. N. Pothos, F. Squitieri, P. Heutink, and J. Xu
DJ-1 Transcriptionally Up-regulates the Human Tyrosine Hydroxylase by Inhibiting the Sumoylation of Pyrimidine Tract-binding Protein-associated Splicing Factor
J. Biol. Chem., July 28, 2006; 281(30): 20940 - 20948.
[Abstract] [Full Text] [PDF]
U. A. Desai, J. Pallos, A. A. K. Ma, B. R. Stockwell, L. M. Thompson, J. L. Marsh, and M. I. Diamond
Biologically active molecules that reduce polyglutamine aggregation and toxicity
Hum. Mol. Genet., July 1, 2006; 15(13): 2114 - 2124.
[Abstract] [Full Text] [PDF]
Z. Qiu, F. Norflus, B. Singh, M. K. Swindell, R. Buzescu, M. Bejarano, R. Chopra, B. Zucker, C. L. Benn, D. P. DiRocco, et al.
Sp1 Is Up-regulated in Cellular and Transgenic Models of Huntington Disease, and Its Reduction Is Neuroprotective
J. Biol. Chem., June 16, 2006; 281(24): 16672 - 16680.
[Abstract] [Full Text] [PDF]
M. Ying, R. Xu, X. Wu, H. Zhu, Y. Zhuang, M. Han, and T. Xu
Sodium Butyrate Ameliorates Histone Hypoacetylation and Neurodegenerative Phenotypes in a Mouse Model for DRPLA
J. Biol. Chem., May 5, 2006; 281(18): 12580 - 12586.
[Abstract] [Full Text] [PDF]
B. E. Morrison, N. Majdzadeh, X. Zhang, A. Lyles, R. Bassel-Duby, E. N. Olson, and S. R. D'Mello
Neuroprotection by histone deacetylase-related protein.
Mol. Cell. Biol., May 1, 2006; 26(9): 3550 - 3564.
[Abstract] [Full Text] [PDF]
A. Bank
Regulation of human fetal hemoglobin: new players, new complexities
Blood, January 15, 2006; 107(2): 435 - 443.
[Abstract] [Full Text] [PDF]
M. Diaz-Hernandez, J. Torres-Peraza, A. Salvatori-Abarca, M. A. Moran, P. Gomez-Ramos, J. Alberch, and J. J. Lucas
Full Motor Recovery Despite Striatal Neuron Loss and Formation of Irreversible Amyloid-Like Inclusions in a Conditional Mouse Model of Huntington's Disease
J. Neurosci., October 19, 2005; 25(42): 9773 - 9781.
[Abstract] [Full Text] [PDF]
T. A. Bolger and T.-P. Yao
Intracellular Trafficking of Histone Deacetylase 4 Regulates Neuronal Cell Death
J. Neurosci., October 12, 2005; 25(41): 9544 - 9553.
[Abstract] [Full Text] [PDF]
M. R. Acharya, A. Sparreboom, J. Venitz, and W. D. Figg
Rational Development of Histone Deacetylase Inhibitors as Anticancer Agents: A Review
Mol. Pharmacol., October 1, 2005; 68(4): 917 - 932.
[Abstract] [Full Text] [PDF]
F. Borovecki, L. Lovrecic, J. Zhou, H. Jeong, F. Then, H. D. Rosas, S. M. Hersch, P. Hogarth, B. Bouzou, R. V. Jensen, et al.
Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease
PNAS, August 2, 2005; 102(31): 11023 - 11028.
[Abstract] [Full Text] [PDF]
S. Q. Harper, P. D. Staber, X. He, S. L. Eliason, I. H. Martins, Q. Mao, L. Yang, R. M. Kotin, H. L. Paulson, and B. L. Davidson
From the Cover: RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model
PNAS, April 19, 2005; 102(16): 5820 - 5825.
[Abstract] [Full Text] [PDF]
M.-C. Chiang, Y.-C. Lee, C.-L. Huang, and Y. Chern
cAMP-response Element-binding Protein Contributes to Suppression of the A2A Adenosine Receptor Promoter by Mutant Huntingtin with Expanded Polyglutamine Residues
J. Biol. Chem., April 8, 2005; 280(14): 14331 - 14340.
[Abstract] [Full Text] [PDF]
N. Agrawal, J. Pallos, N. Slepko, B. L. Apostol, L. Bodai, L.-W. Chang, A.-S. Chiang, L. M. Thompson, and J. L. Marsh
Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila
PNAS, March 8, 2005; 102(10): 3777 - 3781.
[Abstract] [Full Text] [PDF]
B. Zucker, R. Luthi-Carter, J. A. Kama, A. W. Dunah, E. A. Stern, J. H. Fox, D. G. Standaert, A. B. Young, and S. J. Augood
Transcriptional dysregulation in striatal projection- and interneurons in a mouse model of Huntington's disease: neuronal selectivity and potential neuroprotective role of HAP1
Hum. Mol. Genet., January 15, 2005; 14(2): 179 - 189.
[Abstract] [Full Text] [PDF]
G. Gardian, S. E. Browne, D.-K. Choi, P. Klivenyi, J. Gregorio, J. K. Kubilus, H. Ryu, B. Langley, R. R. Ratan, R. J. Ferrante, et al.
Neuroprotective Effects of Phenylbutyrate in the N171-82Q Transgenic Mouse Model of Huntington's Disease
J. Biol. Chem., January 7, 2005; 280(1): 556 - 563.
[Abstract] [Full Text] [PDF]
R. J. Ferrante, H. Ryu, J. K. Kubilus, S. D'Mello, K. L. Sugars, J. Lee, P. Lu, K. Smith, S. Browne, M. F. Beal, et al.
Chemotherapy for the Brain: The Antitumor Antibiotic Mithramycin Prolongs Survival in a Mouse Model of Huntington's Disease
J. Neurosci., November 17, 2004; 24(46): 10335 - 10342.
[Abstract] [Full Text] [PDF]
C. M. Everett and N. W. Wood
Trinucleotide repeats and neurodegenerative disease
Brain, November 1, 2004; 127(11): 2385 - 2405.
[Abstract] [Full Text] [PDF]
S. Ghosh and M. B. Feany
Comparison of pathways controlling toxicity in the eye and brain in Drosophila models of human neurodegenerative diseases
Hum. Mol. Genet., September 15, 2004; 13(18): 2011 - 2018.
[Abstract] [Full Text] [PDF]
D. Helmlinger, S. Hardy, S. Sasorith, F. Klein, F. Robert, C. Weber, L. Miguet, N. Potier, A. Van-Dorsselaer, J.-M. Wurtz, et al.
Ataxin-7 is a subunit of GCN5 histone acetyltransferase-containing complexes
Hum. Mol. Genet., June 15, 2004; 13(12): 1257 - 1265.
[Abstract] [Full Text] [PDF]
M. Minamiyama, M. Katsuno, H. Adachi, M. Waza, C. Sang, Y. Kobayashi, F. Tanaka, M. Doyu, A. Inukai, and G. Sobue
Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy
Hum. Mol. Genet., June 1, 2004; 13(11): 1183 - 1192.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|