Neuroprotective effects of psychotropic drugs in huntington's disease

International Journal of Molecular Sciences

Volumn 14, Issue 11, 2013, Pages 22558-22603

  Lauterbach, Edward C ^a,b  

^a MERCER UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b MERCER UNIVERSITY   (United States)

Author keywords

Animal model; Antidepressant; Antipsychotic; Anxiolytic; Apoptosis; Epigenetics; Gene expression; Huntington's disease; Hypnotic; Mood stabilizer; Neurodegenerative disease

Indexed keywords

ANTIDEPRESSANT AGENT; CYPROHEPTADINE; DESIPRAMINE; DOPAMINE RECEPTOR STIMULATING AGENT; FLUOXETINE; HALOPERIDOL; HYPNOTIC AGENT; IMIPRAMINE; LAMOTRIGINE; LITHIUM; MAPROTILINE; MELATONIN; MICRORNA 222; MOOD STABILIZER; NEUROLEPTIC AGENT; NORTRIPTYLINE; OLANZAPINE; OXCARBAZEPINE; PIMAVANSERIN; PSYCHOTROPIC AGENT; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TETRABENAZINE; TETRACYCLIC ANTIDEPRESSANT AGENT; TRAZODONE; TRICYCLIC ANTIDEPRESSANT AGENT; TRIFLUOPERAZINE; UNINDEXED DRUG; VALPROIC ACID; VENLAFAXINE;

APOPTOSIS; AUTOPHAGY; CELL PROTECTION; CORPUS STRIATUM; DNA METHYLATION; DOSE RESPONSE; DRUG EFFICACY; EPIGENETICS; GENE; GENE EXPRESSION REGULATION; GENE TARGETING; HISTONE ACETYLATION; HISTONE MODIFICATION; HTT GENE; HUMAN; HUNTINGTIN GENE; HUNTINGTON CHOREA; LOW DRUG DOSE; MEMORY; MITOCHONDRIAL RESPIRATION; MOTOR PERFORMANCE; NERVOUS SYSTEM DEVELOPMENT; NEUROPROTECTION; NONHUMAN; ONSET AGE; PHARMACODYNAMICS; PROTEIN AGGREGATION; PROTEIN DNA BINDING; PSYCHOPHARMACOLOGY; REVIEW; RNA EDITING; TISSUE PRESERVATION;

ANIMALS; DISEASE MODELS, ANIMAL; HUMANS; HUNTINGTON DISEASE; MICE; MICRORNAS; NEUROPROTECTIVE AGENTS; PSYCHOTROPIC DRUGS;

EID: 84887522597     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms141122558     Document Type: Review

References (195)

1. Walker, F. O. Huntington's disease. Lancet 2007, 369, 218-228.
2. Chen, C. M. Mitochondrial dysfunction, metabolic deficits, and increased oxidative stress in Huntington's disease. Chang. Gung Med. J. 2011, 34, 135-152.
3. Bano, D.; Zanetti, F.; Mende, Y.; Nicotera, P. Neurodegenerative processes in Huntington's disease. Cell Death Dis. 2011, 2, e228.
4. Bithell, A.; Johnson, R.; Buckley, N. J. Transcriptional dysregulation of coding and non-coding genes in cellular models of Huntington's disease. Biochem. Soc. Trans. 2009, 37, 1270-1275.
5. Lauterbach, E. C.; Cummings, J. L.; Duffy, J.; Coffey, C. E.; Kaufer, D.; Lovell, M.; Malloy, P.; Reeve, A.; Royall, D. R.; Rummans, T. A.; et al. Neuropsychiatric correlates and treatment of lenticulostriatal disease: A review of the literature and overview of research opportunities in Huntington's, Wilson's, and Fahr's diseases. J. Neuropsychiatry Clin. Neurosci. 1998, 10, 249-266.
6. Anderson, K. E.; Marder, K. S. An overview of psychiatric symptoms in Huntington's disease. Curr. Psychiatry Rep. 2001, 3, 379-388.
7. Ranen, N. G. Huntington's Disease. In Psychiatric Management in Neurological Disease; Lauterbach, E. C., Ed.; American Psychiatric Press Group: Washington, DC, USA, 2000; pp. 71-92.
8. Naarding, P.; Kremer, H. P.; Zitman, F. G. Huntington's disease: A review of the literature on prevalence and treatment of neuropsychiatric phenomena. Eur. Psychiatry 2001, 16, 439-445.
9. Lauterbach, E. C. Psychotropic drug effects on gene transcriptomics relevant to Alzheimer's disease. Alzheimer Dis. Assoc. Disord. 2012, 26, 1-7.
10. Lauterbach, E. C. Psychotropic drug effects on gene transcriptomics relevant to Parkinson's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 2012, 38, 107-115.
11. Lauterbach, E. C. Psychotropics regulate Skp1a, Aldh1a1, and Hspa8 transcription-Potential to delay Parkinson's disease. Prog. Neuropsychopharmacol. Biol. Psychiatry 2013, 40, 236-239.
12. Lauterbach, E. C.; Victoroff, J.; Coburn, K. L.; Shillcutt, S. D.; Doonan, S. M.; Mendez, M. F. Psychopharmacological neuroprotection in neurodegenerative disease: Assessing the preclinical data. J. Neuropsychiatry Clin. Neurosci. 2010, 22, 8-18.
13. Lauterbach, E. C.; Shillcutt, S. D.; Victoroff, J.; Coburn, K. L.; Mendez, M. F. Psychopharmacological neuroprotection in neurodegenerative disease: Heuristic clinical applications. J. Neuropsychiatry Clin. Neurosci. 2010, 22, 130-154.
14. Lauterbach, E. C.; Mendez, M. F. Psychopharmacological neuroprotection in neurodegenerative diseases, part III: Criteria-based assessment: A report of the ANPA Committee on Research. J. Neuropsychiatry Clin. Neurosci. 2011, 23, 242-260.
15. Lauterbach, E. C.; Fontenelle, L. F.; Teixeira, A. L. The neuroprotective disease-modifying potential of psychotropics in Parkinson's disease. Parkinsons Dis. 2012, 2012, 753548.
16. Gene Omnibus Expression Profiles. Available online: http://www. ncbi. nlm. nih. gov/geoprofiles (accessed on 25 September 2013).
17. Miller, B. H.; Schultz, L. E.; Gulati, A.; Cameron, M. C.; Pletcher, M. T. Genetic regulation of behavioral and neuronal responses to fluoxetine. Neuropsychopharmacology 2008, 33, 1312-1322.
18. Affymetrix Website. Available online: https://www. affymetrix. com/user/login. jsp?toURL=/analysis/netaffx/xmlquery. affx?netaffx=netaffx4_annot&hightlight=true&rootCategoryId= (accessed on 24 September 2013).
19. Fatemi, S. H.; Reutiman, T. J.; Folsom, T. D.; Bell, C.; Nos, L.; Fried, P.; Pearce, D. A.; Singh, S.; Siderovski, D. P.; Willard, F. S.; et al. Chronic olanzapine treatment causes differential expression of genes in frontal cortex of rats as revealed by DNA microarray technique. Neuropsychopharmacology 2006, 31, 1888-1899.
20. Andresen, J. M.; Gayan, J.; Cherny, S. S.; Brocklebank, D.; Alkorta-Aranburu, G.; Addis, E. A.; The US-Venezuela Collaborative Research Group; Cardon, L. R.; Housman, D. E.; Wexler, N. S. Replication of twelve association studies for Huntington's disease residual age of onset in large Venezuelan kindreds. J. Med. Genet. 2007, 44, 44-50.
21. Vuillaume, I.; Vermersch, P.; Destée, A.; Petit, H.; Sablonnière, B. Genetic polymorphisms adjacent to the CAG repeat influence clinical features at onset in Huntington's disease. J. Neurol. Neurosurg. Psychiatry 1998, 64, 758-762.
22. Chattopadhyay, B.; Ghosh, S.; Gangopadhyay, P. K.; Das, S. K.; Roy, T.; Sinha, K. K.; Jha, D. K.; Mukherjee, S. C.; Chakraborty, A.; Singhal, B. S.; et al. Modulation of age at onset in Huntington's disease and spinocerebellar ataxia type 2 patients originated from eastern India. Neurosci. Lett. 2003, 345, 93-96.
23. Wilburn, B.; Rudnicki, D. D.; Zhao, J.; Weitz, T. M.; Cheng, Y.; Gu, X.; Greiner, E.; Park, C. S.; Wang, N.; Sopher, B. L.; et al. An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice. Neuron 2011, 70, 427-440.
24. Kovtun, I. V.; Liu, Y.; Bjoras, M.; Klungland, A.; Wilson, S. H.; McMurray, C. T. OGG1 initiates age-dependent CAG trinucleotide expansion in somatic cells. Nature 2007, 447, 447-452.
25. Gomes-Pereiram, M.; Monckton, D. G. Chemical modifiers of unstable expanded simple sequence repeats: What goes up, could come down. Mutat. Res. 2006, 598, 15-34.
26. Gusella, J. F.; MacDonald, M. E. Huntington's disease: The case for genetic modifiers. Genome Med. 2009, 1, 80.
27. Kalathur, R. K. R.; Hernández-Prieto, M. A.; Futschik, M. E. Huntington's disease and its therapeutic target genes: A global functional profile based on the HD Research Crossroads database. BMC Neurol. 2012, 12, 47.
28. Buckley, N. J.; Johnson, R.; Zuccato, C.; Bithell, A.; Cattaneo, E. The role of REST in transcriptional and epigenetic dysregulation in Huntington's disease. Neurobiol. Dis. 2010, 39, 28-39.
29. Roy, M.; Leclerc, D.; Wu, Q.; Gupta, S.; Kruger, W. D.; Rozen, R. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency. J. Cell. Biochem. 2008, 105, 467-476.
30. Leclerc, D.; Rozen, R. Endoplasmic reticulum stress increases the expression of methylenetetrahydrofolate reductase through the IRE1 transducer. J. Biol. Chem. 2008, 283, 3151-3160.
31. Yang, Z.; Yin, J. Y.; Gong, Z. C.; Huang, Q.; Chen, H.; Zhang, W.; Zhou, H. H.; Liu, Z. Q. Evidence for an effect of clozapine on the regulation of fat-cell derived factors. Clin. Chim. Acta 2009, 408, 98-104.
32. Kim, K. H.; Song, M. J.; Yoo, E. J.; Choe, S. S.; Park, S. D.; Kim, J. B. Regulatory role of glycogen synthase kinase 3 for transcriptional activity of ADD1/SREBP1c. J. Biol. Chem. 2004, 279, 51999-52006.
33. Chen, W. Y.; Weng, J. H.; Huang, C. C.; Chung, B. C. Histone deacetylase inhibitors reduce steroidogenesis through SCF-mediated ubiquitination and degradation of steroidogenic factor 1 (NR5A1). Mol. Cell. Biol. 2007, 27, 7284-7290.
34. Ishii, T.; Hashimoto, E.; Ukai, W.; Tateno, M.; Yoshinaga, T.; Saito, S.; Sohma, H.; Saito, T. Lithium-induced suppression of transcription repressor NRSF/REST: Effects on the dysfunction of neuronal differentiation by ethanol. Eur. J. Pharmacol. 2008, 593, 36-43.
35. Taylor, P.; Fangusaro, J.; Rajaram, V.; Goldman, S.; Helenowski, I. B.; MacDonald, T.; Hasselblatt, M.; Riedemann, L.; Laureano, A.; Cooper, L.; et al. REST is a novel prognostic factor and therapeutic target for medulloblastoma. Mol. Cancer Ther. 2012, 11, 1713-1723.
36. Kim, S. J.; Lee, B. H.; Lee, Y. S.; Kang, K. S. Defective cholesterol traffic and neuronal differentiation in neural stem cells of Niemann-Pick type C disease improved by valproic acid, a histone deacetylase inhibitor. Biochem. Biophys. Res. Commun. 2007, 360, 593-599.
37. Charvin, D.; Vanhoutte, P.; Pagès, C.; Borrelli, E.; Caboche, J. Unraveling a role for dopamine in Huntington's disease: The dual role of reactive oxygen species and D2 receptor stimulation. Proc. Natl. Acad. Sci. USA 2005, 102, 12218-12223.
38. Carmichael, J.; Sugars, K. L.; Bao, Y. P.; Rubinsztein, D. C. Glycogen synthase kinase-3beta inhibitors prevent cellular polyglutamine toxicity caused by the Huntington's disease mutation. J. Biol. Chem. 2002, 277, 33791-33798.
39. Sarkar, S.; Floto, R. A.; Berger, Z.; Imarisio, S.; Cordenier, A.; Pasco, M.; Cook, L. J.; Rubinsztein, D. C. Lithium induces autophagy by inhibiting inositol monophosphatase. J. Cell. Biol. 2005, 170, 1101-1111.
40. Sarkar, S.; Krishna, G.; Imarisio, S.; Saili, S.; O'Kane, C. J.; Rubinsztein, D. C. A rational mechanism for combination treatment of Huntington's disease using lithium and rapamycin. Hum. Mol. Genet. 2008, 17, 170-178.
41. Sarkar, S.; Rubinsztein, D. C. Inositol and IP3 levels regulate autophagy: Biology and therapeutic speculations. Autophagy 2006, 2, 132-134.
42. Chiu, C. T.; Chuang, D. M. Neuroprotective action of lithium in disorders of the central nervous system. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2011, 36, 461-476.
43. Morselli, E.; Tasdemir, E.; Maiuri, M. C.; Galluzzi, L.; Kepp, O.; Criollo, A.; Vicencio, J. M.; Soussi, T.; Kroemer, G. Mutant p53 protein localized in the cytoplasm inhibits autophagy. Cell Cycle 2008, 7, 3056-3061.
44. Chiu, C. T.; Liu, G.; Leeds, P.; Chuang, D. M. 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.
45. Xiong, N.; Jia, M.; Chen, C.; Xiong, J.; Zhang, Z.; Huang, J.; Hou, L.; Yang, H.; Cao, X.; Liang, Z.; et al. Potential autophagy enhancers attenuate rotenone-induced toxicity in SH-SY5Y. Neuroscience 2011, 199, 292-302.
46. Li, X. Z.; Chen, X. P.; Zhao, K.; Bai, L. M.; Zhang, H.; Zhou, X. Therapeutic effects of valproate combined with lithium carbonate on MPTP-induced Parkinsonism in mice: Possible mediation through enhanced autophagy. Int. J. Neurosci. 2013, 123, 73-79.
47. Peng, Q.; Masuda, N.; Jiang, M.; Li, Q.; Zhao, M.; Ross, C. A.; Duan, W. The antidepressant sertraline improves the phenotype, promotes neurogenesis and increases BDNF levels in the R6/2 Huntington's disease mouse model. Exp. Neurol. 2008, 210, 154-163.
48. Duan, W.; Peng, Q.; Masuda, N.; Ford, E.; Tryggestad, E.; Ladenheim, B.; Zhao, M.; Cadet, J. L.; Wong, J.; Ross, C. A. Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington's disease. Neurobiol. Dis. 2008, 30, 312-322.
49. Ehrnhoefer, D. E.; Butland, S. L.; Pouladi, M. A.; Hayden, M. R. Mouse models of Huntington disease: Variations on a theme. Dis. Models Mech. 2009, 2, 123-129.
50. Ng, C. W.; Yildirim, F.; Yap, Y. S.; Dalin, S.; Matthews, B. J.; Velez, P. J.; Labadorf, A.; Housman, D. E.; Fraenkel, E. Extensive changes in DNA methylation are associated with expression of mutant huntingtin. Proc. Natl. Acad. Sci. USA 2013, 110, 2354-2359.
51. Villar-Menéndez, I.; Blanch, M.; Tyebji, S.; Pereira-Veiga, T.; Albasanz, J. L.; Martín, M.; Ferrer, I.; Pérez-Navarro, E.; Barrachina, M. Increased 5-methylcytosine and decreased 5-hydroxymethylcytosine levels are associated with reduced striatal A2AR levels in Huntington's disease. Neuromol. Med. 2013, 15, 295-309.
52. Lee, J.; Hong, Y. K.; Jeon, G. S.; Hwang, Y. J.; Kim, K. Y.; Seong, K. H.; Jung, M. K.; Picketts, D. J.; Kowall, N. W.; Cho, K. S.; et al. ATRX induction by mutant huntingtin via Cdx2 modulates heterochromatin condensation and pathology in Huntington's disease. Cell Death Differ. 2012, 19, 1109-1116.
53. Urdinguio, R. G.; Sanchez-Mut, J. V.; Esteller, M. Epigenetic mechanisms in neurological diseases: Genes, syndromes, and therapies. Lancet Neurol. 2009, 8, 1056-1072.
54. Kim, M. O.; Chawla, P.; Overland, R. P.; Xia, E.; Sadri-Vakili, G.; Cha, J. H. Altered histone monoubiquitylation mediated by mutant huntingtin induces transcriptional dysregulation. J. Neurosci. 2008, 28, 3947-3957.
55. Yeh, H. H.; Young, D.; Gelovani, J. G.; Robinson, A.; Davidson, Y.; Herholz, K.; Mann, D. M. Histone deacetylase class II and acetylated core histone immunohistochemistry in human brains with Huntington's disease. Brain Res. 2013, 1504, 16-24.
56. Kleiman, R. J.; Kimmel, L. H.; Bove, S. E.; Lanz, T. A.; Harms, J. F.; Romegialli, A.; Miller, K. S.; Willis, A.; des Etages, S.; Kuhn, M.; et al. Chronic suppression of phosphodiesterase 10A alters striatal expression of genes responsible for neurotransmitter synthesis, neurotransmission, and signaling pathways implicated in Huntington's disease. J. Pharmacol. Exp. Ther. 2011, 336, 64-76.
57. Steffan, J. S.; Bodai, L.; Pallos, J.; Poelman, M.; McCampbell, A.; Apostol, B. L.; Kazantsev, A.; Schmidt, E.; Zhu, Y. Z.; Greenwald, M.; et al. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001, 413, 739-743.
58. Steffan, J. S.; Kazantsev, A.; Spasic-Boskovic, O.; Greenwald, M.; Zhu, Y. Z.; Gohler, H.; Wanker, E. E.; Bates, G. P.; Housman, D. E.; Thompson, L. M. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc. Natl. Acad. Sci. USA 2000, 97, 6763-6768.
59. Gardian, G.; Browne, S. E.; Choi, D. K.; Klivenyi, P.; Gregorio, J.; Kubilus, J. K.; Ryu, H.; Langley, B.; Ratan, R. R.; Ferrante, R. J.; et al. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease. J. Biol. Chem. 2005, 280, 556-563.
60. Ferrante, R. J.; Kubilus, J. K.; Lee, J.; Ryu, H.; Beesen, A.; Zucker, B.; Smith, K.; Kowall, N. W.; Ratan, R. R.; Luthi-Carter, R.; et al. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J. Neurosci. 2003, 23, 9418-9127.
61. Stack, E. C.; del Signore, S. J.; Luthi-Carter, R.; Soh, B. Y.; Goldstein, D. R.; Matson, S.; Goodrich, S.; Markey, A. L.; Cormier, K.; Hagerty, S. W.; et al. Modulation of nucleosome dynamics in Huntington's disease. Hum. Mol. Genet. 2007, 16, 1164-1175.
62. Valor, L. M.; Guiretti, D.; Lopez-Atalaya, J. P.; Barco, A. Genomic landscape of transcriptional and epigenetic dysregulation in early onset polyglutamine disease. J. Neurosci. 2013, 33, 10471-10482.
63. Dompierre, J. P.; Godin, J. D.; Charrin, B. C.; Cordelieres, F. P.; King, S. J.; Humbert, S.; Saudou, F. Histone deacetylase 6 inhibition compensates for the transport deficit in Huntington's disease by increasing tubulin acetylation. J. Neurosci. 2007, 27, 3571-3583.
64. Jiang, H.; Poirier, M. A.; Liang, Y.; Pei, Z.; Weiskittel, C. E.; Smith, W. W.; DeFranco, D. B.; Ross, C. A. Depletion of CBP is directly linked with cellular toxicity caused by mutant huntingtin. Neurobiol. Dis. 2006, 23, 543-551.
65. Jeong, H.; Cohen, D. E.; Cui, L.; Supinski, A.; Savas, J. N.; Mazzulli, J. R.; Yates, J. R., III; Bordone, L.; Guarente, L.; Krainc, D. Sirt1 mediates neuroprotection from mutant huntingtin by activation of the TORC1 and CREB transcriptional pathway. Nat. Med. 2011, 18, 159-165.
66. Roze, E.; Betuing, S.; Deyts, C.; Marcon, E.; Brami-Cherrier, K.; Pagès, C.; Humbert, S.; Mérienne, K.; Caboche, J. Mitogen-and stress-activated protein kinase-1 deficiency is involved in expanded-huntingtin-induced transcriptional dysregulation and striatal death. FASEB J. 2008, 22, 1083-1093.
67. Martin, E.; Betuing, S.; Pagès, C.; Cambon, K.; Auregan, G.; Deglon, N.; Roze, E.; Caboche, J. Mitogen-and stress-activated protein kinase 1-induced neuroprotection in Huntington's disease: Role on chromatin remodeling at the PGC-1-alpha promoter. Hum. Mol. Genet. 2011, 20, 2422-2434.
68. Jin, J.; Albertz, J.; Guo, Z.; Peng, Q.; Rudow, G.; Troncoso, J. C.; Ross, C. A.; Duan, W. Neuroprotective effects of PPAR-gamma agonist rosiglitazone in N171-82Q mouse model of Huntington's disease. J. Neurochem. 2013, 125, 410-419.
69. Cui, L.; Jeong, H.; Borovecki, F.; Parkhurst, C. N.; Tanese, N.; Krainc, D. Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006, 127, 59-69.
70. Lee, S. T.; Chu, K.; Jung, K. H.; Im, W. S.; Park, J. E.; Lim, H. C.; Won, C. H.; Shin, S. H.; Lee, S. K.; Kim, M.; et al. Slowed progression in models of Huntington disease by adipose stem cell transplantation. Ann. Neurol. 2009, 66, 671-681.
71. Tsunemi, T.; Ashe, T. D.; Morrison, B. E.; Soriano, K. R.; Au, J.; Roque, R. A.; Lazarowski, E. R.; Damian, V. A.; Masliah, E.; La Spada, A. R. PGC-1alpha rescues Huntington's disease proteotoxicity by preventing oxidative stress and promoting TFEB function. Sci. Transl. Med. 2012, 4, doi: 10. 1126/scitranslmed. 3003799.
72. Chaturvedi, R. K.; Beal, M. F. Mitochondrial diseases of the brain. Free Radic. Biol. Med. 2013, 63, 1-29.
73. Pallàs, M.; Pizarro, J. G.; Gutierrez-Cuesta, J.; Crespo-Biel, N.; Alvira, D.; Tajes, M.; Yeste-Velasco, M.; Folch, J.; Canudas, A. M.; Sureda, F. X.; et al. Modulation of SIRT1 expression in different neurodegenerative models and human pathologies. Neuroscience 2008, 154, 1388-1397.
74. Jiang, M.; Wang, J.; Fu, J.; Du, L.; Jeong, H.; West, T.; Xiang, L.; Peng, Q.; Hou, Z.; Cai, H.; et al. Neuroprotective role of Sirt1 in mammalian models of Huntington's disease through activation of multiple Sirt1 targets. Nat. Med. 2011, 18, 153-158.
75. Fu, J.; Jin, J.; Cichewicz, R. H.; Hageman, S. A.; Ellis, T. K.; Xiang, L.; Peng, Q.; Jiang, M.; Arbez, N.; Hotaling, K.; et al. trans-(-)-ε{lunate}-Viniferin increases mitochondrial sirtuin 3 (SIRT3), activates AMP-activated protein kinase (AMPK), and protects cells in models of Huntington Disease. J. Biol. Chem. 2012, 287, 24460-24472.
76. Sadri-Vakili, G.; Bouzou, B.; Benn, C. L.; Kim, M. O.; Chawla, P.; Overland, R. P.; Glajch, K. E.; Xia, E.; Qiu, Z.; Hersch, S. M.; et al. Histones associated with downregulated genes are hypo-acetylated in Huntington's disease models. Hum. Mol. Genet. 2007, 16, 1293-1306.
77. Ryu, H.; Lee, J.; Hagerty, S. W.; Soh, B. Y.; McAlpin, S. E.; Cormier, K. A.; Smith, K. M.; Ferrante, R. J. ESET/SETDB1 gene expression and histone H3 (K9) trimethylation in Huntington's disease. Proc. Natl. Acad. Sci. USA 2006, 103, 19176-19181.
78. Ferrante, R. J.; Ryu, H.; Kubilus, J. K.; D'Mello, S.; Sugars, K. L.; Lee, J.; Lu, P.; Smith, K.; Browne, S.; Beal, M. F.; 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.
79. Edmunds, J. W.; Mahadevan, L. C.; Clayton, A. L. Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation. EMBO J. 2008, 27, 406-420.
80. Quinti, L.; Chopra, V.; Rotili, D.; Valente, S.; Amore, A.; Franci, G.; Meade, S.; Valenza, M.; Altucci, L.; Maxwell, M. M.; 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, doi: 10. 1371/currents. RRN1172.
81. Hockly, E.; Richon, V. M.; Woodman, B.; Smith, D. L.; Zhou, X.; Rosa, E.; Sathasivam, K.; Ghazi-Noori, S.; Mahal, A.; Lowden, P. A.; 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.
82. Mielcarek, M.; Benn, C. L.; Franklin, S. A.; Smith, D. L.; Woodman, B.; Marks, P. A.; Bates, G. P. 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.
83. Thomas, E. A.; Coppola, G.; Desplats, P. A.; Tang, B.; Soragni, E.; Burnett, R.; Gao, F.; Fitzgerald, K. M.; Borok, J. F.; Herman, D.; 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.
84. Hoshino, M.; Tagawa, K.; Okuda, T.; Murata, M.; Oyanagi, K.; Arai, N.; Mizutani, T.; Kanazawa, I.; Wanker, E. E.; Okazawa, H. Histone deacetylase activity is retained in primary neurons expressing mutant huntingtin protein. J. Neurochem. 2003, 87, 257-267.
85. Chopra, V.; Quinti, L.; Kim, J.; Vollor, L.; Narayanan, K. L.; Edgerly, C.; Cipicchio, P. M.; Lauver, M. A.; Choi, S. H.; Silverman, R. B.; et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models. Cell Rep. 2012, 2, 1492-1497.
86. McConoughey, S. J.; Basso, M.; Niatsetskaya, Z. V.; Sleiman, S. F.; Smirnova, N. A.; Langley, B. C.; Mahishi, L.; Cooper, A. J.; Antonyak, M. A.; Cerione, R. A.; et al. Inhibition of transglutaminase 2 mitigates transcriptional dysregulation in models of Huntington disease. EMBO Mol. Med. 2010, 2, 349-370.
87. Zuccato, C.; Tartari, M.; Crotti, A.; Goffredo, D.; Valenza, M.; Conti, L.; Cataudella, T.; Leavitt, B. R.; Hayden, M. R.; Timmusk, T.; et al. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet. 2003, 35, 76-83.
88. Paschen, W.; Hedreen, J. C.; Ross, C. A. RNA editing of the glutamate receptor subunits GluR2 and GluR6 in human brain tissue. J. Neurochem. 1994, 63, 1596-1602.
89. Akbarian, S.; Smith, M. A.; Jones, E. G. Editing for an AMPA receptor subunit RNA in prefrontal cortex and striatum in Alzheimer's disease, Huntington's disease and schizophrenia. Brain Res. 1995, 699, 297-304.
90. Packer, A. N.; Xing, Y.; Harper, S. Q.; Jones, L.; Davidson, B. L. The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease. J. Neurosci. 2008, 28, 14341-14346.
91. Martí, E.; Pantano, L.; Bañez-Coronel, M.; Llorens, F.; Miñones-Moyano, E.; Porta, S.; Sumoy, L.; Ferrer, I.; Estivill, X. 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.
92. Johnson, R.; Zuccato, C.; Belyaev, N. D.; Guest, D. J.; Cattaneo, E.; Buckley, N. J. A microRNA-based gene dysregulation pathway in Huntington's disease. Neurobiol. Dis. 2008, 29, 438-45.
93. Gaughwin, P. M.; Ciesla, M.; Lahiri, N.; Tabrizi, S. J.; Brundin, P.; Björkqvist, M. Hsa-miR-34b is a plasma-stable microRNA that is elevated in pre-manifest Huntington's disease. Hum. Mol. Genet. 2011, 20, 2225-2237.
94. Jin, J.; Cheng, Y.; Zhang, Y.; Wood, W.; Peng, Q.; Hutchison, E.; Mattson, M. P.; Becker, K. G.; Duan, W. Interrogation of brain miRNA and mRNA expression profiles reveals a molecular regulatory network that is perturbed by mutant huntingtin. J. Neurochem. 2012, 123, 477-490.
95. Sinha, M.; Ghose, J.; Das, E.; Bhattarcharyya, N. P. Altered microRNAs in STHdh(Q111)/Hdh(Q111) cells: MiR-146a targets TBP. Biochem. Biophys. Res. Commun. 2010, 396, 742-747.
96. Lee, S. T.; Chu, K.; Im, W. S.; Yoon, H. J.; Im, J. Y.; Park, J. E.; Park, K. H.; Jung, K. H.; Lee, S. K.; Kim, M.; et al. Altered microRNA regulation in Huntington's disease models. Exp. Neurol. 2011, 227, 172-179.
97. Jovicic, A.; Zaldivar Jolissaint, J. F.; Moser, R.; Silva Santos, M. F.; Luthi-Carter, R. MicroRNA-22 (miR-22) overexpression is neuroprotective via general anti-apoptotic effects and may also target specific Huntington's disease-related mechanisms. PLoS One 2013, 8, e54222.
98. Das, E.; Jana, N. R.; Bhattacharyya, N. P. MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdhQ111/HdhQ111 cells. Biochem. Biophys. Res. Commun. 2013, 437, 217-224.
99. Ghose, J.; Sinha, M.; Das, E.; Jana, N. R.; Bhattacharyya, N. P. Regulation of miR-146a by RelA/NFkB and p53 in STHdh(Q111)/Hdh(Q111) cells, a cell model of Huntington's disease. PLoS One 2011, 6, e23837.
100. Soldati, C.; Bithell, A.; Johnston, C.; Wong, K. Y.; Stanton, L. W.; Buckley, N. J. Dysregulation of REST-regulated coding and non-coding RNAs in a cellular model of Huntington's disease. J. Neurochem. 2013, 124, 418-430.
101. Kozlowska, E.; Krzyzosiak, W. J.; Koscianska, E. Regulation of Huntingtin gene expression by miRNA-137,-214,-148a, and their respective isomiRs. Int. J. Mol. Sci. 2013, 14, 16999-17016.
102. Cheng, P. H.; Li, C. L.; Chang, Y. F.; Tsai, S. J.; Lai, Y. Y.; Chan, A. W.; Chen, C. M.; Yang, S. H. miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models. Am. J. Hum. Genet. 2013, 93, 306-312.
103. Sinha, M.; Mukhopadhyay, S.; Bhattacharyya, N. P. Mechanism(s) of alteration of micro RNA expressions in Huntington's disease and their possible contributions to the observed cellular and molecular dysfunctions in the disease. Neuromol. Med. 2012, 14, 221-243.
104. Bilen, J.; Liu, N.; Burnett, B. G.; Pittman, R. N.; Bonini, N. M. MicroRNA pathways modulate polyglutamine-induced neurodegeneration. Mol. Cell 2006, 24, 157-163.
105. Yazawa, I.; Hazeki, N.; Nakase, H.; Kanazawa, I.; Tanaka, M. Histone H3 is aberrantly phosphorylated in glutamine-repeat diseases. Biochem. Biophys. Res. Commun. 2003, 302, 144-149.
106. Chen, R. W.; Qin, Z. H.; Ren, M.; Kanai, H.; Chalecka-Franaszek, E.; Leeds, P.; Chuang, D. M. Regulation of c-Jun N-terminal kinase, p38 kinase and AP-1 DNA binding in cultured brain neurons: Roles in glutamate excitotoxicity and lithium neuroprotection. J. Neurochem. 2003, 84, 566-575.
107. Acquaah-Mensah, G. K.; Kehrer, J. P.; Leslie, S. W. In utero ethanol suppresses cerebellar activator protein-1 and nuclear factor-kappa B transcriptional activation in a rat fetal alcohol syndrome model. J. Pharmacol. Exp. Ther. 2002, 301, 277-283.
108. Xu, J.; Culman, J.; Blume, A.; Brecht, S.; Gohlke, P. Chronic treatment with a low dose of lithium protects the brain against ischemic injury by reducing apoptotic death. Stroke 2003, 34, 1287-1292.
109. Pacheco, M. A.; Jope, R. S. Modulation of carbachol-stimulated AP-1 DNA binding activity by therapeutic agents for bipolar disorder in human neuroblastoma SH-SY5Y cells. Brain Res. Mol. Brain Res. 1999, 72, 138-146.
110. Ozaki, N.; Chuang, D. M. Lithium increases transcription factor binding to AP-1 and cyclic AMP-responsive element in cultured neurons and rat brain. J. Neurochem. 1997, 69, 2336-2344.
111. Yuan, P. X.; Chen, G.; Huang, L. D.; Manji, H. K. Lithium stimulates gene expression through the AP-1 transcription factor pathway. Brain Res. Mol. Brain Res. 1998, 58, 225-230.
112. Manji, H. K.; Bebchuk, J. M.; Moore, G. J.; Glitz, D.; Hasanat, K. A.; Chen, G. Modulation of CNS signal transduction pathways and gene expression by mood-stabilizing agents: Therapeutic implications. J. Clin. Psychiatry 1999, 60 (Suppl. 2), 27-39; Discussion 40-41, 113-116.
113. Yuan, P.; Chen, G.; Manji, H. K. Lithium activates the c-Jun NH2-terminal kinases in vitro and in the CNS in vivo. J. Neurochem. 1999, 73, 2299-2309.
114. Chen, G.; Masana, M. I.; Manji, H. K. Lithium regulates PKC-mediated intracellular cross-talk and gene expression in the CNS in vivo. Bipolar Disord. 2000, 2, 217-236.
115. Rao, J. S.; Rapoport, S. I.; Bosetti, F. Decrease in the AP-2 DNA-binding activity and in the protein expression of AP-2 alpha and AP-2 beta in frontal cortex of rats treated with lithium for 6 weeks. Neuropsychopharmacology 2005, 30, 2006-2013.
116. Miller, J. C.; Jiménez, P.; Mathé, A. A. Restraint stress influences AP-1 and CREB DNA-binding activity induced by chronic lithium treatment in the rat frontal cortex and hippocampus. Int. J. Neuropsychopharmacol. 2007, 10, 609-619.
117. Gao, X. M.; Fukamauchi, F.; Chuang, D. M. Long-term biphasic effects of lithium treatment on phospholipase C-coupled M3-muscarinic acetylcholine receptors in cultured cerebellar granule cells. Neurochem. Int. 1993, 22, 395-403.
118. Pennypacker, K. R.; Walczak, D.; Thai, L.; Fannin, R.; Mason, E.; Douglass, J.; Hong, J. S. Kainate-induced changes in opioid peptide genes and AP-1 protein expression in the rat hippocampus. J. Neurochem. 1993, 60, 204-211.
119. Kim, H. C.; Pennypacker, K. R.; Bing, G.; Bronstein, D.; McMillian, M. K.; Hong, J. S. The effects of dextromethorphan on kainic acid-induced seizures in the rat. Neurotoxicology 1996, 17, 375-385.
120. Kim, H. C.; Bing, G.; Jhoo, W. K.; Ko, K. H.; Kim, W. K.; Lee, D. C.; Shin, E. J.; Hong, J. S. Dextromethorphan modulates the AP-1 DNA-binding activity induced by kainic acid. Brain Res. 1999, 824, 125-132.
121. Kim, H. C.; Bing, G.; Jhoo, W. K.; Kim, W. K.; Shin, E. J.; Im, D. H.; Kang, K. S.; Ko, K. H. Metabolism to dextrorphan is not essential for dextromethorphan's anticonvulsant activity against kainate in mice. Life Sci. 2003, 72, 769-783.
122. Lee, K. H.; Ahn, J. I.; Yu, D. H.; Koh, H. C.; Kim, S. H.; Yang, B. H.; Lee, Y. S.; Lee, Y. S. Dextromethorphan alters gene expression in rat brain hippocampus and cortex. Int. J. Mol. Med. 2003, 11, 559-568.
123. Anderson, A. N.; Roncaroli, F.; Hodges, A.; Deprez, M.; Turkheimer, F. E. Chromosomal profiles of gene expression in Huntington's disease. Brain 2008, 131, 381-388.
124. Leng, Y.; Fessler, E. B.; Chuang, D. M. Neuroprotective effects of the mood stabilizer lamotrigine against glutamate excitotoxicity: Roles of chromatin remodelling and Bcl-2 induction. Int. J. Neuropsychopharmacol. 2013, 16, 607-620.
125. Onishchenko, N.; Karpova, N.; Sabri, F.; Castrén, E.; Ceccatelli, S. Long-lasting depression-like behavior and epigenetic changes of BDNF gene expression induced by perinatal exposure to methylmercury. J. Neurochem. 2008, 106, 1378-1387.
126. Covington, H. E., 3rd; Vialou, V. F.; LaPlant, Q.; Ohnishi, Y. N.; Nestler, E. J. Hippocampal-dependent antidepressant-like activity of histone deacetylase inhibition. Neurosci. Lett. 2011, 493, 122-126.
127. Rouaux, C.; Panteleeva, I.; René, F.; Gonzalez de Aguilar, J. L.; Echaniz-Laguna, A.; Dupuis, L.; Menger, Y.; Boutillier, A. L.; Loeffler, J. P. Sodium valproate exerts neuroprotective effects in vivo through CREB-binding protein-dependent mechanisms but does not improve survival in an amyotrophic lateral sclerosis mouse model. J. Neurosci. 2007, 27, 5535-5545.
128. Abumaria, N.; Rygula, R.; Hiemke, C.; Fuchs, E.; Havemann-Reinecke, U.; Rüther, E.; Flügge, G. Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat. Eur. Neuropsychopharmacol. 2007, 17, 417-429.
129. Chen, R.-W.; Chuang, D.-M. Long-term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression. J. Biol. Chem. 1999, 274, 6039-6042.
130. Davenport, C. M.; Sevastou, I. G.; Hooper, C.; Pocock, J. M. Inhibiting p53 pathways in microglia attenuates microglial-evoked neurotoxicity following exposure to Alzheimer peptides. J. Neurochem. 2010, 112, 552-563.
131. Mao, C. D.; Hoang, P.; DiCorleto, P. E. Lithium inhibits cell cycle progression and induces stabilization of p53 in bovine aortic endothelial cells. J. Biol. Chem. 2001, 276, 26180-26188.
132. Tasdemir, E.; Maiuri, M. C.; Galluzzi, L.; Vitale, I.; Djavaheri-Mergny, M.; D'Amelio, M.; Criollo, A.; Morselli, E.; Zhu, C.; Harper, F.; et al. Regulation of autophagy by cytoplasmic p53. Nat. Cell Biol. 2008, 10, 676-687.
133. Lu, R.; Song, L.; Jope, R. S. Lithium attenuates p53 levels in human neuroblastoma SH-SY5Y cells. Neuroreport 1999, 10, 1123-1125.
134. Tsui, M. M.; Tai, W. C.; Wong, W. Y.; Hsiao, W. L. Selective G2/M arrest in a p53(Val135)-transformed cell line induced by lithium is mediated through an intricate network of MAPK and β-catenin signaling pathways. Life Sci. 2012, 91, 312-321.
135. Wu, Y.; Shi, X.; Liu, Y.; Zhang, X.; Wang, J.; Luo, X.; Wen, A. Histone deacetylase 1 is required for carbamazepine-induced CYP3A4 expression. J. Pharm. Biomed. Anal. 2012, 58, 78-82.
136. Zhu, Y. F.; Ye, B. G.; Shen, J. Z.; Lin, C. M.; Lin, F. A.; Shen, S. F.; Xu, C. B. Inhibitory effect of VPA on multiple myeloma U266 cell proliferation and regulation of histone acetylation. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2010, 18, 638-641.
137. Liu, S.; Klisovic, R. B.; Vukosavljevic, T.; Yu, J.; Paschka, P.; Huynh, L.; Pang, J.; Neviani, P.; Liu, Z.; Blum, W.; et al. Targeting AML1/ETO-histone deacetylase repressor complex: A novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1/ETO-positive acute myeloid leukemia cells. J. Pharmacol. Exp. Ther. 2007, 321, 953-960.
138. Liu, P.; Tian, X.; Shi, G. R.; Jiang, F. Y.; Liu, B. Q.; Zhang, Z. H.; Zhao, L.; Yan, L. N.; Liang, Z. Q.; Hao, C. L. Inhibitory effect of valproic acid on xenografted Kasumi-1 tumor growth in nude mouse and its mechanism. Zhonghua Xue Ye Xue Za Zhi 2011, 32, 458-462.
139. Hrzenjak, A.; Moinfar, F.; Kremser, M. L.; Strohmeier, B.; Staber, P. B.; Zatloukal, K.; Denk, H. Valproate inhibition of histone deacetylase 2 affects differentiation and decreases proliferation of endometrial stromal sarcoma cells. Mol. Cancer Ther. 2006, 5, 2203-2210.
140. Vallo, S.; Xi, W.; Hudak, L.; Juengel, E.; Tsaur, I.; Wiesner, C.; Haferkamp, A.; Blaheta, R. A. HDAC inhibition delays cell cycle progression of human bladder cancer cells in vitro. Anticancer Drugs 2011, 22, 1002-1009.
141. Mao, X.; Hou, T.; Cao, B.; Wang, W.; Li, Z.; Chen, S.; Fei, M.; Hurren, R.; Gronda, M.; Wu, D.; et al. The tricyclic antidepressant amitriptyline inhibits D-cyclin transactivation and induces myeloma cell apoptosis by inhibiting histone deacetylases: In vitro and in silico evidence. Mol. Pharmacol. 2011, 79, 672-680.
142. Ookubo, M.; Kanai, H.; Aoki, H.; Yamada, N. Antidepressants and mood stabilizers effects on histone deacetylase expression in C57BL/6 mice: Brain region specific changes. J. Psychiatr. Res. 2013, 47, 1204-1214.
143. Calabrese, F.; Luoni, A.; Guidotti, G.; Racagni, G.; Fumagalli, F.; Riva, M. A. Modulation of neuronal plasticity following chronic concomitant administration of the novel antipsychotic lurasidone with the mood stabilizer valproic acid. Psychopharmacology (Berl.) 2013, 226, 101-112.
144. Bradbury, C. A.; Khanim, F. L.; Hayden, R.; Bunce, C. M.; White, D. A.; Drayson, M. T.; Craddock, C.; Turner, B. M. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia 2005, 19, 1751-1759.
145. Cassel, S.; Carouge, D.; Gensburger, C.; Anglard, P.; Burgun, C.; Dietrich, J. B.; Aunis, D.; Zwiller, J. Fluoxetine and cocaine induce the epigenetic factors MeCP2 and MBD1 in adult rat brain. Mol. Pharmacol. 2006, 70, 487-492.
146. Hunsberger, J. G.; Fessler, E. B.; Chibane, F. L.; Leng, Y.; Maric, D.; Elkahloun, A. G.; Chuang, D. M. Mood stabilizer-regulated miRNAs in neuropsychiatric and neurodegenerative diseases: Identifying associations and functions. Am. J. Transl. Res. 2013, 5, 450-464.
147. Sinha, M.; Ghose, J.; Bhattarcharyya, N. P. Micro RNA-214,-150,-146a and-125b target Huntingtin gene. RNA Biol. 2011, 8, 1005-1021.
148. Melo, C. A.; Drost, J.; Wijchers, P. J.; van de Werken, H.; de Wit, E.; Oude Vrielink, J. A. F.; Elkon, R.; Melo, S. A.; Léveill, N.; Kalluri, R.; et al. eRNAs are required for p53-dependent enhancer activity and gene transcription. Mol. Cell 2012, 49, 524-535.
149. Benchoua, A.; Trioulier, Y.; Diguet, E.; Malgorn, C.; Gaillard, M. C.; Dufour, N.; Elalouf, J. M.; Krajewski, S.; Hantraye, P.; Déglon, N.; et al. Dopamine determines the vulnerability of striatal neurons to the N-terminal fragment of mutant huntingtin through the regulation of mitochondrial complex II. Hum. Mol. Genet. 2008, 17, 1446-1456.
150. Tang, T. S.; Slow, E.; Lupu, V.; Stavrovskaya, I. G.; Sugimori, M.; Llinás, R.; Kristal, B. S.; Hayden, M. R.; Bezprozvanny, I. Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. Proc. Natl. Acad. Sci. USA 2005, 102, 2602-2607.
151. Kumar, P.; Kumar, A. Possible role of sertraline against 3-nitropropionic acid induced behavioral, oxidative stress and mitochondrial dysfunctions in rat brain. Prog. Neuropsychopharmacol. Biol. Psychiatry 2009, 33, 100-108.
152. Kumar, P.; Kalonia, H.; Kumar, A. Nitric oxide mechanism in the protective effect of antidepressants against 3-nitropropionic acid-induced cognitive deficit, glutathione and mitochondrial alterations in animal model of Huntington's disease. Behav. Pharmacol. 2010, 21, 217-230.
153. Kumar, P.; Kalonia, H.; Kumar, A. Novel protective mechanisms of antidepressants against 3-nitroproprionic acid induced Huntington's-like symptoms: A comparative study. J. Psychopharmacol. 2011, 25, 1399-1411.
154. Wang, X.; Sirianni, A.; Pei, Z.; Cormier, K.; Smith, K.; Jiang, J.; Zhou, S.; Wang, H.; Zhao, R.; Yano, H.; et al. The melatonin MT1 receptor axis modulates mutant Huntingtin-mediated toxicity. J. Neurosci. 2011, 31, 14496-14507.
155. Sarantos, M. R.; Papanikolaou, T.; Ellerby, L. M.; Hughes, R. E. Pizotifen activates ERK and provides neuroprotection in vitro and in vivo in models of Huntington's disease. J. Huntington's Dis. 2012, 1, 195-210.
156. Senatorov, V. V.; Ren, M.; Kanai, H.; Wei, H.; Chuang, D. M. Short-term lithium treatment promotes neuronal survival and proliferation in rat striatum infused with quinolinic acid, an excitotoxic model of Huntington's disease. Mol. Psychiatry 2004, 9, 371-385.
157. Pouladi, M. A.; Brillaud, E.; Xie, Y.; Conforti, P.; Graham, R. K.; Ehrnhoefer, D. E.; Franciosi, S.; Zhang, W.; Poucheret, P.; Compte, E.; et al. NP03, a novel low-dose lithium formulation, is neuroprotective in the YAC128 mouse model of Huntington disease. Neurobiol. Dis. 2012, 48, 282-289.
158. Yasuda, S.; Liang, M. H.; Marinova, Z.; Yahyavi, A.; Chuang, D. M. The mood stabilizers lithium and valproate selectively activate the promoter IV of brain-derived neurotrophic factor in neurons. Mol. Psychiatry 2009, 14, 51-59.
159. Grote, H. E.; Bull, N. D.; Howard, M. L.; van Dellen, A.; Blakemore, C.; Bartlett, P. F.; Hannan, A. J. Cognitive disorders and neurogenesis deficits in Huntington's disease mice are rescued by fluoxetine. Eur. J. Neurosci. 2005, 22, 2081-2088.
160. Zuccato, C.; Marullo, M.; Vitali, B.; Tarditi, A.; Mariotti, C.; Valenza, M.; Lahiri, N.; Wild, E. J.; Sassone J.; Ciammola, A.; et al. Brain-derived neurotrophic factor in patients with Huntington's disease. PLoS One 2011, 6, e22966.
161. Charvin, D.; Roze, E.; Perrin, V.; Deyts, C.; Betuing, S.; Pagès, C.; Régulier, E.; Luthi-Carter, R.; Brouillet, E.; Déglon, N.; et al. Haloperidol protects striatal neurons from dysfunction induced by mutated huntingtin in vivo. Neurobiol. Dis. 2008, 29, 22-29.
162. Tang, T. S.; Chen, X.; Liu, J.; Bezprozvanny, I. Dopaminergic signaling and striatal neurodegeneration in Huntington's disease. J. Neurosci. 2007, 27, 7899-7910.
163. Wang, H.; Chen, X.; Li, Y.; Tang, T. S.; Bezprozvanny, I. Tetrabenazine is neuroprotective in Huntington's disease mice. Mol. Neurodegener. 2010, 5, 18.
164. Crespo-Biel, N.; Camins, A.; Pallas, M.; Canudas, A. M. Evidence of calpain/cdk5 pathway inhibition by lithium in 3-nitropropionic acid toxicity in vivo and in vitro. Neuropharmacology 2009, 56, 422-428.
165. Wood, N. I.; Morton, A. J. Chronic lithium chloride treatment has variable effects on motor behaviour and survival of mice transgenic for the Huntington's disease mutation. Brain Res. Bull. 2003, 61, 375-383.
166. Zádori, D.; Geisz, A.; Vamos, E.; Vecsei, L.; Klivenyi, P. Valproate ameliorates the survival and the motor performance in a transgenic mouse model of Huntington's disease. Pharmacol. Biochem. Behav. 2009, 94, 148-153.
167. Wang, H.; Guan, Y.; Wang, X.; Smith, K.; Cormier, K.; Zhu, S.; Stavrovskaya, I. G.; Huo, C.; Ferrante, R. J.; Kristal, B. S.; et al. Nortriptyline delays disease onset in models of chronic neurodegeneration. Eur. J. Neurosci. 2007, 26, 633-641.
168. Cheng, Y.; Peng, Q.; Hou, Z.; Aggarwal, M.; Zhang, J.; Mori, S.; Ross, C. A.; Duan, W. Structural MRI detects progressive regional brain atrophy and neuroprotective effects in N171-92Q Huntington's disease mouse model. Neuroimage 2011, 56, 1027-1034.
169. Aggarwal, M.; Duan, W.; Hou, Z.; Rakesh, N.; Peng, Q.; Ross, C. A.; Miller, M. I.; Mori, S.; Zhang, J. Spatiotemporal mapping of brain atrophy in mouse models of Huntington's disease using longitudinal in vivo magnetic resonance imaging. Neuroimage 2012, 60, 2086-2095.
170. Danivas, V.; Moily, N. S.; Thimmaiah, R.; Muralidharan, K.; Purushotham, M.; Muthane, U.; Jain, S. Off label use of lithium in the treatment of Huntington's disease: A case series. Indian J. Psychiatry 2013, 55, 81-83.
171. Clinical Trials. gov. Available online: http://www. ClinicalTrials. gov (accessed on 25 September 2013).
172. Mestre, T.; Ferreira, J.; Coelho, M. M.; Rosa, M.; Sampaio, C. Therapeutic interventions for disease progression in Huntington's disease. Cochrane Database Syst. Rev. 2009, doi: 10. 1002/14651858. CD006455. pub2.
173. Kremer, B.; Clark, C. M.; Almqvist, E. W.; Raymond, L. A.; Graf, P.; Jacova, C.; Mezei, M.; Hardy, M. A.; Snow, B.; Martin, W.; et al. Influence of lamotrigine on progression of early Huntington disease: A randomized clinical trial. Neurology 1999, 53, 1000-1011.
174. Huntington Study Group DOMINO Investigators. A futility study of minocycline in Huntington's disease. Mov. Disord. 2010, 25, 2219-2224.
175. Shoulson, I.; Odoroff, C.; Oakes, D.; Behr, J.; Goldblatt, D.; Caine, E.; Kennedy, J.; Miller, C.; Bamford, K.; Rubin, A.; et al. A controlled clinical trial of baclofen as protective therapy in early Huntington's disease. Ann. Neurol. 1989, 25, 252-259.
176. Landwehrmeyer, G. B.; Dubois, B.; de Yébenes, J. G.; Kremer, B.; Gaus, W.; Kraus, P. H.; Przuntek, H.; Dib, M.; Doble, A.; Fischer, W.; et al. Riluzole in Huntington's disease: A 3-year, randomized controlled study. Ann. Neurol. 2007, 62, 262-272.
177. Puri, B. K.; Leavitt, B. R.; Hayden, M. R.; Ross, C. A.; Rosenblatt, A.; Greenamyre, J. T.; Hersch, S.; Vaddadi, K. S.; Sword, A.; Horrobin, D. F.; et al. Ethyl-EPA in Huntington disease: A double-blind, randomized, placebo-controlled trial. Neurology 2005, 65, 286-292.
178. The Huntington study group. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001, 57, 397-404.
179. Ranen, N. G.; Peyser, C. E.; Coyle, J. T.; Bylsma, F. W.; Sherr, M.; Day, L.; Folstein, M. F.; Brandt, J.; Ross, C. A.; Folstein, S. E. A controlled trial of idebenone in Huntington's disease. Mov. Disord. 1996, 11, 549-554.
180. Verbessem, P.; Lemiere, J.; Eijnde, B. O.; Swinnen, S.; Vanhees, L.; van Leemputte, M.; Hespel, P.; Dom, R. Creatine supplementation in Huntington's disease: A placebo-controlled pilot trial. Neurology 2003, 61, 925-930.
181. Lauterbach, E. C. Use of psychotropic medication in Alzheimer's disease is associated with more rapid cognitive and functional decline. Evid. Based Med. 2013, doi: 10. 1136/eb-2013-101225.
182. Weir, D. W.; Sturrock, A.; Leavitt, B. R. Development of biomarkers for Huntington's disease. Lancet Neurol. 2011, 10, 573-590.
183. Paulsen, J. S.; Langbehn, D. R.; Stout, J. C.; Aylward, E.; Ross, C. A.; Nance, M.; Guttman, M.; Johnson, S.; MacDonald, M.; Beglinger, L. J.; et al. Detection of Huntington's disease decades before diagnosis: The predict-HD study. J. Neurol. Neurosurg. Psychiatry 2008, 79, 874-880.
184. Tabrizi, S. J.; Scahill, R. I.; Durr, A.; Roos, R. A.; Leavitt, B. R.; Jones, R.; Landwehrmeyer, G. B.; Fox, N. C.; Johnson, H.; Hicks, S. L.; et al. Biological and clinical changes in premanifest and early stage Huntington's disease in the TRACK-HD study: The 12-month longitudinal analysis. Lancet Neurol. 2011, 10, 31-42.
185. Hu, Y.; Chopra, V.; Chopra, R.; Locascio, J. J.; Liao, Z.; Ding, H.; Zheng, B.; Matson, W. R.; Ferrante, R. J.; Rosas, H. D.; et al. Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse. Proc. Natl. Acad. Sci. USA 2011, 108, 17141-17146.
186. Georgiou-Karistianis, N.; Scahill, R.; Tabrizi, S. J.; Squitieri, F.; Aylward, E. Structural MRI in Huntington's disease and recommendations for its potential use in clinical trials. Neurosci. Biobehav. Rev. 2013, 37, 480-490.
187. Aylward, E. H.; Sparks, B. F.; Field, K. M.; Yallapragada, V.; Shpritz, B. D.; Rosenblatt, A.; Brandt, J.; Gourley, L. M.; Liang, K.; Zhou, H.; et al. Onset and rate of striatal atrophy in preclinical Huntington disease. Neurology 2004, 63, 66-72.
188. Van Den Bogaard, S. J. A.; Dumas, E. M.; Acharya, T. P.; Johnson, H.; Langbehn, D. R.; Scahill, R. I.; Tabrizi, S. J.; van Buchem, M. A.; van Der Grond, J.; Roos, R. A. C. Early atrophy of pallidum and accumbens nucleus in Huntington's disease. J. Neurol. 2011, 258, 412-420.
189. Aylward, E. H.; Nopoulos, P. C.; Ross, C. A.; Langbehn, D. R.; Pierson, R. K.; Mills, J. A.; Johnson, H. J.; Magnotta, V. A.; Juhl, A. R.; Paulsen, J. S. Longitudinal change in regional brain volumes in prodromal Huntington disease. J. Neurol. Neurosurg. Psychiatry 2011, 82, 405-410.
190. Tabrizi, S. J.; Reilmann, R.; Roos, R. A.; Durr, A.; Leavitt, B.; Owen, G.; Jones, R.; Johnson, H.; Craufurd, D.; Hicks, S. L.; et al. Potential endpoints for clinical trials in premanifest and early Huntington's disease in the TRACK-HD study: Analysis of 24 month observational data. Lancet Neurol. 2012, 11, 42-53.
191. Ruocco, H. H.; Bonilha, L.; Li, L. M.; Lopes-Cendes, I.; Cendes, F. Longitudinal analysis of regional grey matter loss in Huntington disease: Effects of the length of the expanded CAG repeat. J. Neurol. Neurosurg. Psychiatry 2008, 79, 130-135.
192. Majid, D. S.; Aron, A. R.; Thompson, W.; Sheldon, S.; Hamza, S.; Stoffers, D.; Holland, D.; Goldstein, J.; Corey-Bloom, J.; Dale, A. M. Basal ganglia atrophy in prodromal Huntington's disease is detectable over one year using automated segmentation. Mov. Disord. 2011, 26, 2544-2551.
193. Hobbs, N. Z.; Henley, S. M.; Ridgway, G. R.; Wild, E. J.; Barker, R. A.; Scahill, R. I.; Barnes, J.; Fox, N. C.; Tabrizi, S. J. The progression of regional atrophy in premanifest and early Huntington's disease: A longitudinal voxel-based morphometry study. J. Neurol. Neurosurg. Psychiatry 2010, 81, 756-763.
194. Aylward, E. H.; Li, Q.; Stine, O. C.; Ranen, N.; Sherr, M.; Barta, P. E.; Bylsma, F. W.; Pearlson, G. D.; Ross, C. A. Longitudinal change in basal ganglia volume in patients with Huntington's disease. Neurology 1997, 48, 394-399.
195. Henley, S. M. D.; Wild, E. J.; Hobbs, N. Z.; Scahill, R. I.; Ridgway, G. R.; MacManus, D. G.; Barker, R. A.; Fox, N. C.; Tabrizi, S. J. Relationship between CAG repeat length and brain volume in premanifest and early Huntington's disease. J. Neurol. 2009, 256, 203-212.