What have we learned from gene expression profiles in Huntington's disease?

Neurobiology of Disease

Volumn 45, Issue 1, 2012, Pages 83-98

  Seredenina, Tamara ^a   Luthi Carter, Ruth ^a  

^a EPFL   (Switzerland)

Author keywords

Biomarker; Blood; Cortex; Huntingtin; Microarray; Muscle; Polyglutamine disease; Striatum; Transcriptomic profiling

Indexed keywords

ACYLTRANSFERASE; ALPHA ACTININ 2; ARGONAUTE 2 PROTEIN; BRAIN DERIVED NEUROTROPHIC FACTOR; CELL NUCLEUS RECEPTOR; CONTACTIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; DNA BINDING PROTEIN; HISTONE DEACETYLASE INHIBITOR; MICRORNA; NUCLEAR FACTOR Y; NUCLEAR FACTOR YA; NUCLEAR FACTOR YB; NUCLEAR FACTOR YC; POSTSYNAPTIC DENSITY PROTEIN 95; PROTEIN P300; REGULATOR PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR BCL11B; TRANSCRIPTION FACTOR BRN2; TRANSCRIPTION FACTOR CTIP2; TRANSCRIPTION FACTOR SIN3A; TRANSCRIPTION FACTOR SP1; TRANSFERRIN BINDING PROTEIN; UNCLASSIFIED DRUG;

BINDING AFFINITY; CELL AGGREGATION; CHROMATIN STRUCTURE; DIAGNOSTIC ACCURACY; DISEASE ACTIVITY; DISEASE ASSOCIATION; DISEASE COURSE; DOWN REGULATION; ENZYME ACTIVITY; GENE ACTIVATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE INTERACTION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC MODEL; HISTONE ACETYLATION; HUMAN; HUNTINGTON CHOREA; INTRACELLULAR SIGNALING; MOLECULAR DIAGNOSIS; MOLECULAR DYNAMICS; NEUROPROTECTION; NONHUMAN; PATHOLOGY; PHARMACOGENOMICS; PREDICTIVE VALUE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN PROCESSING; REGULATOR GENE; REVIEW; TRANSCRIPTION REGULATION; TRANSLATION REGULATION;

ANIMALS; BRAIN; DISEASE MODELS, ANIMAL; GENE EXPRESSION; GENE EXPRESSION PROFILING; HUMANS; HUNTINGTON DISEASE;

EID: 81955162960     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2011.07.001     Document Type: Review

References (180)

1. Andre V.M., et al. Dopamine and glutamate in Huntington's disease: a balancing act. CNS Neurosci. Ther. 2010, 16:163-178.
2. Antonini A., et al. Striatal glucose metabolism and dopamine D2 receptor binding in asymptomatic gene carriers and patients with Huntington's disease. Brain 1996, 119(Pt 6):2085-2095.
3. Apostol B.L., et al. Mutant huntingtin alters MAPK signaling pathways in PC12 and striatal cells: ERK1/2 protects against mutant huntingtin-associated toxicity. Hum. Mol. Genet. 2006, 15:273-285.
4. Arlotta P., et al. Ctip2 controls the differentiation of medium spiny neurons and the establishment of the cellular architecture of the striatum. J. Neurosci. 2008, 28:622-632.
5. Arning L., et al. NR2A and NR2B receptor gene variations modify age at onset in Huntington disease. Neurogenetics 2005, 6:25-28.
6. Augood S.J., et al. Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease. Ann. Neurol. 1997, 42:215-221.
7. Avram D., et al. COUP-TF (chicken ovalbumin upstream promoter transcription factor)-interacting protein 1 (CTIP1) is a sequence-specific DNA binding protein. Biochem. J. 2002, 368:555-563.
8. Bae B.I., et al. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005, 47:29-41.
9. Beal M.F., Ferrante R.J. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat. Rev. Neurosci. 2004, 5:373-384.
10. Becanovic K., et al. Transcriptional changes in Huntington disease identified using genome-wide expression profiling and cross-platform analysis. Hum. Mol. Genet. 2010, 19:1438-1452.
11. Benn C.L., et al. Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease. Hum. Mol. Genet. 2005, 14:3065-3078.
12. Benn C.L., et al. Huntingtin modulates transcription, occupies gene promoters in vivo, and binds directly to DNA in a polyglutamine-dependent manner. J. Neurosci. 2008, 28:10720-10733.
13. Benn C.L., et al. Environmental enrichment reduces neuronal intranuclear inclusion load but has no effect on messenger RNA expression in a mouse model of Huntington disease. J. Neuropathol. Exp. Neurol. 2010, 69:817-827.
14. Bilen J., et al. A new role for microRNA pathways: modulation of degeneration induced by pathogenic human disease proteins. Cell Cycle. 2006, 5:2835-2838.
15. Blazquez C., et al. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease. Brain 2011, 134:119-136.
16. Blum D., et al. A dual role of adenosine A2A receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A2A antagonists. J. Neurosci. 2003, 23:5361-5369.
17. Borovecki F., et al. Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease. Proc. Natl. Acad. Sci. U. S. A. 2005, 102:11023-11028.
18. Boudreau R.L., et al. Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol. Ther. 2009, 17:1053-1063.
19. Boutell J., et al. Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. Hum. Mol. Genet. 1999, 8:1647-1655.
20. Brown T.B., et al. Neocortical expression of mutant huntingtin is not required for alterations in striatal gene expression or motor dysfunction in a transgenic mouse. Hum. Mol. Genet. 2008, 17:3095-3104.
21. Butler R., Bates G.P. Histone deacetylase inhibitors as therapeutics for polyglutamine disorders. Nat. Rev. Neurosci. 2006, 7:784-796.
22. Carmichael J., et al. Glycogen synthase kinase-3beta inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation. J. Biol. Chem. 2002, 277:33791-33798.
23. Cattaneo E., et al. Normal huntingtin function: an alternative approach to Huntington's disease. Nat. Rev. Neurosci. 2005, 6:919-930.
24. Cepeda C., et al. Increased GABAergic function in mouse models of Huntington's disease: reversal by BDNF. J. Neurosci. Res. 2004, 78:855-867.
25. Cha J.H. Transcriptional signatures in Huntington's disease. Prog. Neurobiol. 2007, 83:228-248.
26. Cha J.H., et al. Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 1999, 354:981-989.
27. Chan E.Y., et al. Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease. Hum. Mol. Genet. 2002, 11:1939-1951.
28. Chaturvedi R.K., et al. Impaired PGC-1alpha function in muscle in Huntington's disease. Hum. Mol. Genet. 2009, 18:3048-3065.
29. Chen-Plotkin A.S., et al. Decreased association of the transcription factor Sp1 with genes downregulated in Huntington's disease. Neurobiol. Dis. 2006, 22:233-241.
30. Chou A.H., et al. Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation. Neurobiol. Dis. 2008, 31:89-101.
31. Cong S.Y., et al. Mutant huntingtin represses CBP, but not p300, by binding and protein degradation. Mol. Cell. Neurosci. 2005, 30:12-23.
32. Cornett J., et al. Polyglutamine expansion of huntingtin impairs its nuclear export. Nat. Genet. 2005, 37:198-204.
33. Crittenden J.R., et al. CalDAG-GEFI down-regulation in the striatum as a neuroprotective change in Huntington's disease. Hum. Mol. Genet. 2010, 19:1756-1765.
34. Crocker S.F., et al. DNA microarray analysis of striatal gene expression in symptomatic transgenic Huntington's mice (R6/2) reveals neuroinflammation and insulin associations. Brain Res. 2006, 1088:176-186.
35. Cui L., et al. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006, 127:59-69.
36. Davies S., et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997, 90:537-548.
37. Davies J.E., et al. The ubiquitin proteasome system in Huntington's disease and the spinocerebellar ataxias. BMC Biochem. 2007, 8(Suppl. 1):S2.
38. Denovan-Wright E.M., Robertson H.A. Cannabinoid receptor messenger RNA levels decrease in a subset of neurons of the lateral striatum, cortex and hippocampus of transgenic Huntington's disease mice. Neuroscience 2000, 98:705-713.
39. Desplats P.A., et al. Selective deficits in the expression of striatal-enriched mRNAs in Huntington's disease. J. Neurochem. 2006, 96:743-757.
40. Desplats P.A., et al. Functional roles for the striatal-enriched transcription factor, Bcl11b, in the control of striatal gene expression and transcriptional dysregulation in Huntington's disease. Neurobiol. Dis. 2008, 31:298-308.
41. Dhaenens C.M., et al. A genetic variation in the ADORA2A gene modifies age at onset in Huntington's disease. Neurobiol. Dis. 2009, 35:474-476.
42. DiFiglia M., et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997, 277:1990-1993.
43. Drouet V., et al. Sustained effects of nonallele-specific Huntingtin silencing. Ann. Neurol. 2009, 65:276-285.
44. Dunah A.W., et al. Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
45. Eulalio A., et al. P-body formation is a consequence, not the cause, of RNA-mediated gene silencing. Mol. Cell. Biol. 2007, 27:3970-3981.
46. Faber P.W., et al. Huntingtin interacts with a family of WW domain proteins. Hum. Mol. Genet. 1998, 7:1463-1474.
47. Falk J., et al. F3/contactin, a neuronal cell adhesion molecule implicated in axogenesis and myelination. Biol Cell. 2002, 94:327-334.
48. Ferrante R.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.
49. Ferrante R.J., et al. Chemotherapy for the brain: the antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease. J. Neurosci. 2004, 24:10335-10342.
50. Ferre S., et al. The striopallidal neuron: a main locus for adenosine-dopamine interactions in the brain. J. Neurosci. 1993, 13:5402-5406.
51. Finkbeiner S., Mitra S. The ubiquitin-proteasome pathway in Huntington's disease. ScientificWorldJournal 2008, 8:421-433.
52. Futter M., et al. Wild-type but not mutant huntingtin modulates the transcriptional activity of liver X receptors. J. Med. Genet. 2009, 46:438.
53. Gambazzi L., et al. Diminished activity-dependent brain-derived neurotrophic factor expression underlies cortical neuron microcircuit hypoconnectivity resulting from exposure to mutant huntingtin fragments. J. Pharmacol. Exp. Ther. 2010, 335:13-22.
54. Gardian G., et al. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease. J. Biol. Chem. 2005, 280:556-563.
55. Gharami K., et al. Brain-derived neurotrophic factor over-expression in the forebrain ameliorates Huntington's disease phenotypes in mice. J. Neurochem. 2008, 105:369-379.
56. Giorgini F., et al. Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J. Biol. Chem. 2008, 283:7390-7400.
57. Glass M., et al. Loss of cannabinoid receptors in the substantia nigra in Huntington's disease. Neuroscience 1993, 56:523-527.
58. Godin J.D., et al. Mutant huntingtin-impaired degradation of beta-catenin causes neurotoxicity in Huntington's disease. EMBO J. 2010, 29:2433-2445.
59. Goldstrohm A.C., et al. The transcription elongation factor CA150 interacts with RNA polymerase II and the pre-mRNA splicing factor SF1. Mol. Cell. Biol. 2001, 21:7617-7628.
60. Greer P.L., Greenberg M.E. From synapse to nucleus: calcium-dependent gene transcription in the control of synapse development and function. Neuron 2008, 59:846-860.
61. Gu X., et al. Pathological cell-cell interactions elicited by a neuropathogenic form of mutant Huntingtin contribute to cortical pathogenesis in HD mice. Neuron 2005, 46:433-444.
62. Gu X., et al. Pathological cell-cell interactions are necessary for striatal pathogenesis in a conditional mouse model of Huntington's disease. Mol. Neurodegener. 2007, 2:8.
63. Han J., et al. RGS2 determines short-term synaptic plasticity in hippocampal neurons by regulating Gi/o-mediated inhibition of presynaptic Ca2+ channels. Neuron 2006, 51:575-586.
64. Hazeki N., et al. Ultrastructure of nuclear aggregates formed by expressing an expanded polyglutamine. Biochem. Biophys. Res. Commun. 2002, 294:429-440.
65. Helmlinger D., et al. Transcriptional alterations and chromatin remodeling in polyglutamine diseases. Trends Genet. 2006, 22:562-570.
66. Hockly E., et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc.Natl. Acad. Sci. U. S. A. 2003, 100:2041-2046.
67. Hodges A., et al. Regional and cellular gene expression changes in human Huntington's disease brain. Hum. Mol. Genet. 2006, 15:965-977.
68. Hodges A., et al. Brain gene expression correlates with changes in behavior in the R6/1 mouse model of Huntington's disease. Genes Brain Behav. 2008, 7:288-299.
69. Holbert S., et al. The Gln-Ala repeat transcriptional activator CA150 interacts with huntingtin: neuropathologic and genetic evidence for a role in Huntington's disease pathogenesis. Proc. Natl. Acad. Sci. U. S. A. 2001, 98:1811-1816.
70. Houten S.M., Auwerx J. PGC-1alpha: turbocharging mitochondria. Cell 2004, 119:5-7.
71. Huang C.C., et al. Amyloid formation by mutant huntingtin: threshold, progressivity and recruitment of normal polyglutamine proteins. Somat. Cell Mol. Genet. 1998, 24:217-233.
72. Huntington's Disease Collaborative Research Group, T. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993, 72:971-983.
73. Igarashi S., et al. Inducible PC12 cell model of Huntington's disease shows toxicity and decreased histone acetylation. Neuroreport 2003, 14:565-568.
74. Illuzzi J., et al. DNA breakage and induction of DNA damage response proteins precede the appearance of visible mutant huntingtin aggregates. J. Neurosci. Res. 2009, 87:733-747.
75. Ingi T., et al. Dynamic regulation of RGS2 suggests a novel mechanism in G-protein signaling and neuronal plasticity. J. Neurosci. 1998, 18:7178-7188.
76. Iwamoto K., et al. Genomic organization and alternative transcripts of the human PQBP-1 gene. Gene 2000, 259:69-73.
77. Jacobsen J.C., et al. HD CAG-correlated gene expression changes support a simple dominant gain of function. Hum. Mol. Genet. 2011, 20(14):2846-2860.
78. Jo K., et al. Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J. Neurosci. 1999, 19:4189-4199.
79. Johnson R., Buckley N.J. Gene dysregulation in Huntington's disease: REST, microRNAs and beyond. Neuromolecular Med. 2009, 11:183-199.
80. Johnson R., et al. A microRNA-based gene dysregulation pathway in Huntington's disease. Neurobiol. Dis. 2008, 29:438-445.
81. Kaltenbach L., et al. Huntingtin interacting proteins are genetic modifiers of neurodegeneration. PLoS Genet. 2007, 3:e82.
82. Kazantsev A.G., Thompson L.M. Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. Nat. Rev. Drug Discov. 2008, 7:854-868.
83. Kazantsev A., et al. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc. Natl. Acad. Sci. U. S. A. 1999, 96:11404-11409.
84. Kazantsev A., et al. A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and pathogenesis in Drosophila. Nat. Genet. 2002, 30:367-376.
85. Kegel K.B., et al. Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. J. Biol. Chem. 2002, 277:7466-7476.
86. Kim M.O., et al. Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulation. J. Neurosci. 2008, 28:3947-3957.
87. Kotliarova S., et al. Decreased expression of hypothalamic neuropeptides in Huntington disease transgenic mice with expanded polyglutamine-EGFP fluorescent aggregates. J. Neurochem. 2005, 93:641-653.
88. Kuhn A., 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. 2007, 16:1845-1861.
89. Labbadia J., et al. Altered chromatin architecture underlies progressive impairment of the heat shock response in mouse models of Huntington disease. J. Clin. Invest. 2011, 121:3306-3319.
90. Landles C., Bates G.P. Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series. EMBO Rep. 2004, 5:958-963.
91. Lau P., Hudson L.D. MicroRNAs in neural cell differentiation. Brain Res. 2010, 1338:14-19.
92. Lee J.M., et al. Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism. PLoS Genet. 2007, 3:e135.
93. Lee S.T., et al. Altered microRNA regulation in Huntington's disease models. Exp. Neurol. 2011, 227:172-179.
94. Li S.H., et al. Interaction of Huntington disease protein with transcriptional activator Sp1. Mol. Cell. Biol. 2002, 22:1277-1287.
95. Lin J., et al. Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGC-1alpha null mice. Cell 2004, 119:121-135.
96. Luthi-Carter R. Huntington's and other polyglutamine diseases: many effects of single gene mutations. Drug Discov Today Dis. Mech. 2007, 4:111-119.
97. Luthi-Carter R., Cha C.J.J. Mechanisms of transcriptional dysregulation in Huntington's disease. Clin. Neurosci. Res. 2003, 3:165-177.
98. Luthi-Carter R., et al. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum. Mol. Genet. 2000, 9:1259-1271.
99. Luthi-Carter R., et al. Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain. Hum. Mol. Genet. 2002, 11:1911-1926.
100. Luthi-Carter R., et al. Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects. Hum. Mol. Genet. 2002, 11:1927-1937.
101. Luthi-Carter R., et al. Complex alteration of NMDA receptors in transgenic Huntington's disease mouse brain: analysis of mRNA and protein expression, plasma membrane association, interacting proteins, and phosphorylation. Neurobiol. Dis. 2003, 14:624-636.
102. Luthi-Carter R., et al. SIRT2 inhibition achieves neuroprotection by decreasing sterol biosynthesis. Proc. Natl. Acad. Sci. U. S. A. 2010, 107:7927-7932.
103. Lynch G., et al. Brain-derived neurotrophic factor restores synaptic plasticity in a knock-in mouse model of Huntington's disease. J. Neurosci. 2007, 27:4424-4434.
104. Maher P., et al. ERK activation by the polyphenols fisetin and resveratrol provides neuroprotection in multiple models of Huntington's disease. Hum. Mol. Genet. 2011, 20:261-270.
105. Mai A., et al. Identification of 4-hydroxyquinolines inhibitors of p300/CBP histone acetyltransferases. Bioorg. Med. Chem. Lett. 2009, 19:1132-1135.
106. Marti E., et al. A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing. Nucleic Acids Res. 2010, 38:7219-7235.
107. McCampbell A., et al. CREB-binding protein sequestration by expanded polyglutamine. Hum. Mol. Genet. 2000, 9:2197-2202.
108. McConoughey S.J., et al. Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease. EMBO Mol. Med. 2010, 2:349-370.
109. Miller B.H., Wahlestedt C. MicroRNA dysregulation in psychiatric disease. Brain Res. 2010, 1338:89-99.
110. Milnerwood A.J., et al. Early development of aberrant synaptic plasticity in a mouse model of Huntington's disease. Hum. Mol. Genet. 2006, 15:1690-1703.
111. Morton A.J., et al. A combination drug therapy improves cognition and reverses gene expression changes in a mouse model of Huntington's disease. Eur. J. Neurosci. 2005, 21:855-870.
112. Morton A.J., et al. Paradoxical delay in the onset of disease caused by super-long CAG repeat expansions in R6/2 mice. Neurobiol. Dis. 2009, 33:331-341.
113. Nickel B.E., et al. Ubiquitinated histone H2B is preferentially located in transcriptionally active chromatin. Biochemistry 1989, 28:958-963.
114. Nishihara E., et al. Nuclear receptor coregulators are new players in nervous system development and function. Mol. Neurobiol. 2004, 30:307-325.
115. Nucifora F.C., et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 2001, 291:2423-2428.
116. Obrietan K., Hoyt K.R. CRE-mediated transcription is increased in Huntington's disease transgenic mice. J. Neurosci. 2004, 24:791-796.
117. Okazawa H., et al. Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. Neuron 2002, 34:701-713.
118. Packer A.N., et al. The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease. J. Neurosci. 2008, 28:14341-14346.
119. Pallos J., 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.
120. Peters L., Meister G. Argonaute proteins: mediators of RNA silencing. Mol Cell. 2007, 26:611-623.
121. Phan J., et al. Adipose tissue dysfunction tracks disease progression in two Huntington's disease mouse models. Hum. Mol. Genet. 2009, 18:1006-1016.
122. Potenza R.L., et al. Adenosine A(2A) receptors modulate BDNF both in normal conditions and in experimental models of Huntington's disease. Purinergic Signal. 2007, 3:333-338.
123. Qiu Z., et al. Sp1 is up-regulated in cellular and transgenic models of Huntington disease, and its reduction is neuroprotective. J. Biol. Chem. 2006, 281:16672-16680.
124. Quinti L., et al. Evaluation of histone deacetylases as drug targets in Huntington's disease models. Study of HDACs in brain tissues from R6/2 and CAG140 knock-in HD mouse models and human patients and in a neuronal HD cell model. PLoS Curr. 2010, 2.
125. Ravache M., et al. Transcriptional activation of REST by Sp1 in Huntington's disease models. PLoS One. 2010, 5:e14311.
126. Rona-Voros K., Weydt P. The role of PGC-1alpha in the pathogenesis of neurodegenerative disorders. Curr. Drug Targets 2010, 11:1262-1269.
127. Rudinskiy N., et al. Diminished hippocalcin expression in Huntington's disease (HD) brain does not account for increased striatal neuron vulnerability as assessed in primary neuron models of HD 2009.
128. Runne H., et al. Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood. Proc. Natl. Acad. Sci. U. S. A. 2007, 104:14424-14429.
129. Runne H., et al. Dysregulation of gene expression in primary neuron models of Huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. J. Neurosci. 2008, 28:9723-9731.
130. Ryu H., et al. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease. Proc. Natl. Acad. Sci. U. S. A. 2006, 103:19176-19181.
131. Sadri-Vakili G., Cha J.H. Histone deacetylase inhibitors: a novel therapeutic approach to Huntington's disease (complex mechanism of neuronal death). Curr. Alzheimer Res. 2006, 3:403-408.
132. Sadri-Vakili G., et al. Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models. Hum. Mol. Genet. 2007, 16:1293-1306.
133. Salim S., et al. Identification of RGS2 and type V adenylyl cyclase interaction sites. J. Biol. Chem. 2003, 278:15842-15849.
134. Savas J.N., et al. Huntington's disease protein contributes to RNA-mediated gene silencing through association with Argonaute and P bodies. Proc. Natl. Acad. Sci. U. S. A. 2008, 105:10820-10825.
135. Schratt G. microRNAs at the synapse. Nat. Rev. Neurosci. 2009, 10:842-849.
136. Seo H., et al. Proteasome activator enhances survival of Huntington's disease neuronal model cells. PLoS One. 2007, 2:e238.
137. Seong I.S., et al. Huntingtin facilitates polycomb repressive complex 2. Hum. Mol. Genet. 2010, 19:573-583.
138. Seredenina T., et al. Decreased Striatal RGS2 Expression Is Neuroprotective in Huntington's Disease (HD) and Exemplifies a Compensatory Aspect of HD-Induced Gene Regulation. PLoS One 2011, 6:e22231.
139. Shimohata T., et al. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nat. Genet. 2000, 26:29-36.
140. Shimojo M. Huntingtin regulates RE1-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) nuclear trafficking indirectly through a complex with REST/NRSF-interacting LIM domain protein (RILP) and dynactin p150 Glued. J. Biol. Chem. 2008, 283:34880-34886.
141. Sinha M., et al. Altered microRNAs in STHdh(Q111)/Hdh(Q111) cells: miR-146a targets TBP. Biochem. Biophys. Res. Commun. 2010, 396:742-747.
142. Sinnarajah S., et al. RGS2 regulates signal transduction in olfactory neurons by attenuating activation of adenylyl cyclase III. Nature 2001, 409:1051-1055.
143. Sipione S., et al. Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses. Hum. Mol. Genet. 2002, 11:1953-1965.
144. Sleiman S.F., et al. Putting the 'HAT' back on survival signalling: the promises and challenges of HDAC inhibition in the treatment of neurological conditions. Expert. Opin. Investig. Drugs. 2009, 18:573-584.
145. Stack E.C., et al. Modulation of nucleosome dynamics in Huntington's disease. Hum. Mol. Genet. 2007, 16:1164-1175.
146. Steffan J.S., et al. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. U. S. A. 2000, 97:6763-6768.
147. Steffan J.S., et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001, 413:739-743.
148. Strand A., et al. Gene expression in Huntington's disease skeletal muscle: a potential biomarker. Hum. Mol. Genet. 2005, 14:1863-1876.
149. Strand A.D., et al. Expression profiling of Huntington's disease models suggests that brain-derived neurotrophic factor depletion plays a major role in striatal degeneration. J. Neurosci. 2007, 27:11758-11768.
150. Strehlow A.N., et al. Wild-type huntingtin participates in protein trafficking between the Golgi and the extracellular space. Hum. Mol. Genet. 2007, 16:391-409.
151. Subramaniam S., et al. Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity. Science 2009, 324:1327-1330.
152. Subramaniam S., et al. Rhes, a physiologic regulator of sumoylation, enhances cross-sumoylation between the basic sumoylation enzymes E1 and Ubc9. J. Biol. Chem. 2010, 285:20428-20432.
153. Sugars K.L., et al. Decreased cAMP response element-mediated transcription: an early event in exon 1 and full-length cell models of Huntington's disease that contributes to polyglutamine pathogenesis. J. Biol. Chem. 2004, 279:4988-4999.
154. Suhr S.T., et al. Identities of sequestered proteins in aggregates from cells with induced polyglutamine expression. J. Cell. Biol. 2001, 153:283-294.
155. Taherzadeh-Fard E., et al. PGC-1alpha as modifier of onset age in Huntington disease. Mol. Neurodegener. 2009, 4:10.
156. Takano H., Gusella J. 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.
157. Tang B., et al. Gene expression profiling of R6/2 transgenic mice with different CAG repeat lengths reveals genes associated with disease onset and progression in Huntington's disease. Neurobiol. Dis. 2011, 42:459-467.
158. Thomas E.A., et al. The HDAC inhibitor 4b ameliorates the disease phenotype and transcriptional abnormalities in Huntington's disease transgenic mice. Proc. Natl. Acad. Sc.i U. S. A. 2008, 105:15564-15569.
159. Thomas E.A., et al. In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons. Hum. Mol. Genet. 2011, 20:1049-1060.
160. Thu D.C., et al. Cell loss in the motor and cingulate cortex correlates with symptomatology in Huntington's disease. Brain 2010, 133:1094-1110.
161. Usdin M.T., et al. Impaired synaptic plasticity in mice carrying the Huntington's disease mutation. Hum. Mol. Genet. 1999, 8:839-846.
162. Wang X., et al. Functional interaction of monoubiquitinated FANCD2 and BRCA2/FANCD1 in chromatin. Mol. Cell. Biol. 2004, 24:5850-5862.
163. Waragai M., et al. PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. Hum. Mol. Genet. 1999, 8:977-987.
164. Weydt P., et al. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metab. 2006, 4:349-362.
165. Weydt P., et al. The gene coding for PGC-1 modifies age at onset in Huntington's disease. Mol. Neurodegener. 2009, 4:3.
166. Wheeler V.C., et al. Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice. Hum. Mol. Genet. 2002, 11:633-640.
167. Wyszynski M., et al. Competitive binding of alpha-actinin and calmodulin to the NMDA receptor. Nature 1997, 385:439-442.
168. Wyttenbach A., et al. Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington's disease. Hum. Mol. Genet. 2001, 10:1829-1845.
169. Yamanaka T., et al. Mutant huntingtin reduces HSP70 expression through the sequestration of NF-Y transcription factor. EMBO J. 2008, 27:827-839.
170. Yamanaka T., et al. Mutant huntingtin fragment selectively suppresses Brn-2 POU domain transcription factor to mediate hypothalamic cell dysfunction. Hum. Mol. Genet. 2010, 19:2099-2112.
171. Yohrling G., et al. Mutant huntingtin increases nuclear corepressor function and enhances ligand-dependent nuclear hormone receptor activation. Mol. Cell. Neurosci. 2003, 23:28-38.
172. Zhai W., et al. In vitro analysis of huntingtin-mediated transcriptional repression reveals multiple transcription factor targets. Cell 2005, 123:1241-1253.
173. Zhang H., et al. Elucidating a normal function of huntingtin by functional and microarray analysis of huntingtin-null mouse embryonic fibroblasts. BMC Neurosci. 2008, 9:38.
174. Zuccato C., et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001, 293:493-498.
175. Zuccato C., et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet. 2003, 35:76-83.
176. Zuccato C., et al. Progressive loss of BDNF in a mouse model of Huntington's disease and rescue by BDNF delivery. Pharmacol. Res. 2005, 52:133-139.
177. Zuccato C., et al. Widespread disruption of repressor element-1 silencing transcription factor/neuron-restrictive silencer factor occupancy at its target genes in Huntington's disease. J. Neurosci. 2007, 27:6972-6983.
178. Zuccato C., et al. Systematic assessment of BDNF and its receptor levels in human cortices affected by Huntington's disease. Brain Pathol. 2008, 18:225-238.
179. Zucker B., et al. 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. 2005, 14:179-189.
180. Zucker B., et al. Decreased Lin7b expression in layer 5 pyramidal neurons may contribute to impaired corticostriatal connectivity in Huntington disease. J. Neuropathol. Exp. Neurol. 2010, 69:880-895.