Molecular Pathogenesis and Therapeutic Targets in Huntington's Disease

Genetic Instabilities and Neurological Diseases

Volumn , Issue , 2006, Pages 223-249

  Bett, John S ^a   Bates, Gillian P ^a   Hockly, Emma ^a  

^a GUY S HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84878455107     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1016/B978-012369462-1/50015-6     Document Type: Chapter

References (198)

1. Bates G.P., Harper P.S., Jones A.L. Huntington's Disease 2002, Oxford University Press, Oxford.
2. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993, 72:971-983. Huntington's Disease Collaborative Research Group.
3. Li S.H., Li X.J. Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet. 2004, 20:146-154.
4. Zuccato C., Ciammola A., Rigamonti D., Leavitt B.R., Goffredo D., Conti L., MacDonald M.E., Friedlander R.M., Silani V., Hayden M.R., Timmusk T., Sipione S., Cattaneo E. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001, 293:493-498.
5. Gauthier L.R., Charrin B.C., Borrell-Pages M., Dompierre J.P., Rangone H., Cordelieres F.P., De Mey J., MacDonald M.E., Lessmann V., Humbert S., Saudou F. Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 2004, 118:127-138.
6. Dragatsis I., Levine M.S., Zeitlin S. Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat. Genet. 2000, 26:300-306.
7. Duyao M.P., Auerbach A.B., Ryan A., Persichetti F., Barnes G.T., McNeil S.M., Ge P., Vonsattel J.P., Gusella J.F., Joyner A.L., et al. Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 1995, 269:407-410.
8. Wexler N.S., Young A.B., Tanzi R.E., Travers H., Starosta-Rubinstein S., Penney J.B., Snodgrass S.R., Shoulson I., Gomez F., Ramos Arroyo M.A., et al. Homozygotes for Huntington's disease. Nature 1987, 326:194-197.
9. Myers R.H., Leavitt J., Farrer L.A., Jagadeesh J., McFarlane H., Mastromauro C.A., Mark R.J., Gusella J.F. Homozygote for Huntington disease. Am. J. Hum. Genet. 1989, 45:615-618.
10. Mangiarini L., Sathasivam K., Seller M., Cozens B., Harper A., Hetherington C., Lawton M., Trottier Y., Lehrach H., Davies S.W., Bates G.P. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 1996, 87:493-506.
11. Bates G. Huntingtin aggregation and toxicity in Huntington's disease. Lancet 2003, 361:1642-1644.
12. Wellington C.L., Singaraja R., Ellerby L., Savill J., Roy S., Leavitt B., Cattaneo E., Hackam A., Sharp A., Thornberry N., Nicholson D.W., Bredesen D.E., Hayden M.R. Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J. Biol. Chem. 2000, 275:19831-19838.
13. Kim Y.J., Yi Y., Sapp E., Wang Y., Cuiffo B., Kegel K.B., Qin Z.H., Aronin N., DiFiglia M. Caspase 3-cleaved N-terminal fragments of wild-type and mutant huntingtin are present in normal and Huntington's disease brains, associate with membranes, and undergo calpain-dependent proteolysis. Proc. Natl. Acad. Sci. USA 2001, 98:12784-12789.
14. Lunkes A., Lindenberg K.S., Ben-Haiem L., Weber C., Devys D., Landwehrmeyer G.B., Mandel J.L., Trottier Y. Proteases acting on mutant huntingtin generate, cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol. Cell 2002, 10:259-269.
15. Bence N.F., Sampat R.M., Kopito R.R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001, 292:1552-1555.
16. Gunawardena S., Golstein L.S. Polyglutamine diseases and transport problems: Deadly traffic jams on neuronal highways. Arch. Neurol. 2005, 62:46-51.
17. Luthi-Carter R., Cha J.-H.J. Mechanisms of transcriptional dysregulation in Huntington's disease. Clin. Neurosci. Res. 2003, 3:165-177.
18. Hockly E., Woodman B., Mahal A., Lewis C.M., Bates G. Standardization and statistical approaches to therapeutic trials in the R6/2 mouse. Brain Res. Bull. 2003, 61:469-479.
19. Davies S.W., Turmaine M., Cozens B.A., DiFiglia M., Sharp A.H., Ross C.A., Scherzinger E., Wanker E.E., Mangiarini L., Bates G.P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997, 90:537-548.
20. DiFiglia M., Sapp E., Chase K.O., Davies S.W., Bates G.P., Vonsattel J.P., Aronin N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997, 277:1990-1993.
21. Scherzinger E., Lurz R., Turmaine M., Mangiarini L., Hollenbach B., Hasenbank R., Bates G.P., Davies S.W., Lehrach H., Wanker E.E. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 1997, 90:549-558.
22. Perutz M.F., Johnson T., Suzuki M., Finch J.T. Glutamine repeats as polar zippers: Their possible role in inherited neurodegenerative diseases. Proc. Natl. Acad. Sci. USA 1994, 91:5355-5358.
23. Kazantsev A., Preisinger E., Dranovsky A., Goldgaber D., Housman D. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc. Natl. Acad. Sci. USA 1999, 96:11404-11409.
24. Scherzinger E., Sittler A., Schweiger K., Heiser V., Lurz R., Hasenbank R., Bates G.P., Lehrach H., Wanker E.E. Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington's disease pathology. Proc. Natl. Acad. Sci. USA 1999, 96:4604-4609.
25. Wacker J.L., Zareie M.H., Fong H., Sarikaya M., Muchowski P.J. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monemer. Nat. Struct. Mol. Biol. 2004, 11:1215-1222.
26. Krobitsch S., Lindquist S. Aggregation of huntingtin in yeast varies, with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc. Natl. Acad. Sci. USA 2000, 97:1589-1594.
27. Faber P.W., Alter J.R., MacDonald M.E., Hart A.C. Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc. Natl. Acad. Sci. USA 1999, 96:179-184.
28. Satyal S.H., Schmidt E., Kitagawa K., Sondheimer N., Lindquist S., Kramer J.M., Morimoto R.I. Polyglutamine aggregates alter protein folding homeostasis in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 2000, 97:5750-5755.
29. Parker J.A., Connolly J.B., Wellington C., Hayden M., Dausset J., Neri C. Expanded polyglutamines in Caenorhabditis elegans cause axonal abnormalities and severe dysfunction of PLM mechanosensory neurons without cell death. Proc Natl. Acad. Sci. USA 2001, 98:13318-13323.
30. Jackson G.R., Salecker I., Dong X., Yao X., Arnheim N., Faber P.W., MacDonald M.E., Zipursky S.L. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 1998, 21:633-642.
31. Kazemi-Esfarjani P., Benzer S. Genetic suppression of polyglutamine toxicity in Drosophila. Science 2000, 287:1837-1840.
32. Marsh J.L., Walker H., Theisen H., Zhu Y.Z., Fielder T., Purcell J., Thompson L.M. Expanded polyglutamine peptides alone are intrinsically cytotoxic and cause, neurodegeneration in Drosophila. Hum. Mol. Genet. 2000, 9:13-25.
33. Yang W., Dunlap J.R., Andrews R.B., Wetzel R. Aggregated polyglutamine peptides delivered to nuclei are, toxic to mammalian cells. Hum. Mol. Genet. 2002, 11:2905-2917.
34. Saudou F., Finkbeiner S., Devys D., Greenberg M.E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 1998, 95:55-66.
35. Arrasate M., Mitra S., Schweitzer E.S., Segal M.R., Finkbeiner S. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 2004, 431:805-810.
36. Kopito R.R. Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 2000, 10:524-530.
37. Schaffar G., Breuer P., Boteva R., Behrends C., Tzvetkov N., Strippel N., Sakahira H., Siegers K., Hayer-Hartl M., Hartl F.U. Cellular toxicity of polyglutamine expansion proteins: Mechanism of transcription factor deactivation. Mol. Cell 2004, 15:95-105.
38. Li H., Li S.H., Cheng A.L., Mangiarini L., Bates G.P., Li X.J. Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice. Hum. Mol. Genet. 1999, 8:1227-1236.
39. Yamamoto A., Lucas J.J., Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 2000, 101:57-66.
40. Kazantsev A., Walker H.A., Slepko N., Bear J.E., Preisinger E., Steffan J.S., Zhu Y.Z., Gertler F.B., Housman D.E., Marsh J.L., Thompson L.M. A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and pathogenesis in Drosophila. Nat. Genet. 2002, 30:367-376.
41. Kennedy L., Evans E., Chen C.M., Craven L., Detloff P.J., Ennis M., Shelbourne P.F. Dramatic tissue-specific mutation length increases are an early molecular event in Huntington disease, pathogenesis. Hum. Mol. Genet. 2003, 12:3359-3367.
42. Tagawa K., Hoshino M., Okuda T., Ueda H., Hayashi H., Engemann S., Okado H., Ichikawa M., Wanker E.E., Okazawa H. Distinct aggregation and cell death patterns among different types of primary neurons induced by mutant huntingtin protein. J. Neurochem. 2004, 89:974-987.
43. Gafni J., Hermel E., Young J.E., Wellington C.L., Hayden M.R., Ellerby L.M. Inhibition of calpain cleavage of huntingtin reduces toxicity: Accumulation of calpain/caspase fragments in the nucleus. J. Biol. Chem. 2004, 279:20211-20220.
44. Hackam A.S., Singaraja R., Wellington C.L., Metzler M., McCutcheon K., Zhang T., Kalchman M., Hayden M.R. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J. Cell Biol. 1998, 141:1097-1105.
45. Martindale D., Hackam A., Wieczorek A., Ellerby L., Wellington C., McCutcheon K., Singaraja R., Kazemi-Esfarjani P., Devon R., Kim S.U., Bredesen D.E., Tufaro F., Hayden M.R. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat. Genet. 1998, 18:150-154.
46. Lunkes A., Mandel J.L. A cellular model that recapitulates major pathogenic steps of Huntington's disease. Hum. Mol. Genet. 1998, 7:1355-1361.
47. Hackam A.S., Singaraja R., Zhang T., Gan L., Hayden M.R. In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington's disease. Hum. Mol. Genet. 1999, 8:25-33.
48. Li H., Li S.H., Johnston H., Shelbourne P.F., Li X.J. Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat. Genet. 2000, 25:385-389.
49. 2-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity. J. Cell Biol. 2003, 163:109-118.
50. Lin C.H., Tallaksen-Greene S., Chien W.M., Cearley J.A., Jackson W.S., Crouse A.B., Ren S., Li X.J., Albin R.L., Detloff P.J. Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum. Mo. Genet. 2001, 10:137-144.
51. Shellbourne P.F., Killeen N., Hevner R.F., Johnston H.M., Tecott L., Lewandoski M., Ennis M., Ramirez L., Li Z., Iannicola C., Littman D.R., Myers R.M. A Huntington's disease CAG expansion at the murine Hdh locus is unstable and associated with behavioural abnormalities in mice. Hum. Mol Genet. 1999, 8:763-774.
52. Jana N.R., Tanaka M., Wang G., Nukina N. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: Their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet. 2000, 9:2009-2018.
53. Hay D.G., Sathasivam K., Tobaben S., Stahl B., Marber M., Metril R., Mahal A., Smith D.L., Woodman B., Bates G.P. Progressive decrease in chaperone protein levels in a mouse model of Huntington's disease and induction of stress proteins as a therapeutic approach. Hum. Mol Genet. 2004, 13:1389-1405.
54. Cummings C.J., Mancini M.A., Antalffy B., DeFrenco D.B., Orr H.T., Zoghbi H.Y. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat. Genet. 1998, 19:148-154.
55. Chai Y., Koppenhafer S.L., Bonini N.M., Paulson H.L. Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. J. Neurosci. 1999, 19:10338-10347.
56. Schmidt T., Lindenberg K.S., Krebs A., Schols L., Laccone F., Herms J., Rechsteiner M., Riess O., Landwehrmeyer G.B. Protein surveillance machinery in brains with spinocerebellar ataxia type 3: Redistribution and differential recruitment of 26S proteasome subunits and chaperones to neuronal intranuclear inclusions. Ann. Neurol. 2002, 51:302-310.
57. Wyttenbach A., Sauvageot O., Carmichael J., Diaz-Latoud C., Arrigo A.P., Rubinsztein D.C. Heat shock protein 27 prevents cellular polyglutamine toxicity and suppresses the increase of reactive oxygen species caused by huntingtin. Hum. Mol. Genet. 2002, 11:1137-1151.
58. Zhou H., Li S.H., Li X.J. Chaperone suppression of cellular toxicity of huntingtin is independent of polygltamine aggregation. J. Biol. Chem. 2001, 276:48417-48424.
59. Kobayashi Y., Kume A., Li M., Doyu M., Hata M., Ohtsuka K., Sobue G. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated andsrogen receptor protein with expanded polyglutamine tract. J. Biol. Chem. 2000, 275:8772-8778.
60. Sittler A., Lurz R., Lueder G., Priller J., Lehrach H., Hayer-Hartl M.K., Hartl F.U., Wanker E.E. Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease. Hum. Mol. Genet. 2001, 10:1307-1315.
61. Warrick J.M., Chan H.Y., Gray-Board G.L., Chai Y., Paulson H.L., Bonini N.M. Suppression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 1999, 23:425-428.
62. Chan H.Y., Warrick J.M., Gray-Board G.L., Paulson H.L., Bonini N.M. Mechanisms of chaperone suppression of polyglutamine disease: Selectivity, synergy and modulation of protein solubility in Drosophila. Hum. Mol Genet. 2000, 9:2811-2820.
63. Muchowski P.J., Schaffar G., Sittler A., Wanker E.E., Hayer-Hartl M.K., Hartl F.U. Hsp70 and hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc. Natl. Acad. Sci. USA 2000, 97:7841-7846.
64. Cummings C.J., Sun Y., Opal P., Antalffy B., Mestril R., Orr H.T., Dillmann W.H., Zoghbi H.Y. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum. Mol Genet. 2001, 10:1511-1518.
65. Adachi H., Katsuno M., Minamiyama M., Sang C., Pagoulatos G., Angelidis C., Kusakabe M., Yoshiki A., Kaboayashi Y., Doyu M., Sobue G. Heat shock protein 70 chaperone overexpression ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model by reducing nuclear-localized mutant androgen receptor protein. J. Neurosci. 2003, 23:2203-2211.
66. Hansson O., Nylandsted J., Castilho R.F., Leist M., Jaattela M., Brundin P. Overexpression of heat shock protein 70 in R6/2 Huntington's disease mice has only modest effects on disease progression. Brain Res. 2003, 970:47-57.
67. Westerheide S.D., Bosman J.D., Mbadugha B.N., Kawahara T.L., Matsumoto G., Kim S., Gu W., Devlin J.P., Silverman R.B., Morimoto R.I. Celastrols as inducers of the heat shock response and cytoprotection. J. Biol. Chem. 2004, 279:56053-56060.
68. Verhoef L.G., Lindsten K., Masucci M.G., Dantuma N.P. Aggregate formation inhibits proteasomal degradation of polyglutamine proteins. Hum. Mol Genet. 2002, 11:2689-2700.
69. Goellner G.M., Rechsteiner M. Are Huntington's and polyglutamine-based ataxias proteasome storage diseases?. Int. J. Biochem. Cell Biol. 2003, 35:562-571.
70. Venkatraman P., Wetzel R., Tanaka M., Nukina N., Goldberg A.L. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol. Cell 2004, 14:95-104.
71. Jana N.R., Zemskov E.A., Wang G., Nukina N. Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Hum. Mol Genet. 2001, 10:1049-1059.
72. Holmberg C.I., Staniszewski K.E., Mensah K.N., Matouschek A., Morimoto R.I. Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J. 2004, 23:4307-4318.
73. Bennett E.J., Bence N.F., Jayakumar R., Kopito R.R. Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol. Cell 2005, 17:351-365.
74. Park Y., Hong S., Kim S.J., Kang S. Proteasome function is inhibited by polyglutamine-expanded ataxin-1, the SCA1 gene product. Mol. Cell 2005, 19:23-30.
75. Diaz-Hernandez M., Hernandez F., Martin-Aparicio E., Gomez-Ramos P., Moran M.A., Castano J.G., Ferrer I., Avila J., Lucas J.J. Neuronal induction of the immunoproteasome in Huntington's disease. J. Neurosci. 2003, 23:11653-11661.
76. Bowman A.B., Yoo S.Y., Dantuma N.P., Zoghbi H.Y. Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of neculear inclusion formation. Hum. Mol. Genet. 2005, 14:679-691.
77. Seo H., Sonntag K.C., Isacson O. Generalized brain and skin proteasome inhibition in Huntington's disease. Ann. Neurol. 2004, 56:319-328.
78. Cummings C.J., Reinstein E., Sun Y., Antalffy B., Jiang Y., Ciechanover A., Orr H.T., Beaudet A.L., Zoghbi H.Y. Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron 1999, 24:879-892.
79. Nollen E.A., Garcia S.M., van Haaften G., Kim S., Chavez A., Morimoto R.I., Plasterk R.H. Genome-wide RNA interference screen identifies previously underscribed regulators of polyglutamine aggregation. Proc. Natl. Acad. Sci. USA 2004, 101:6403-6408.
80. Warrick J.M., Morabito L.M., Bilen J., Gordesky-Gold B., Faust L.Z., Paulson H.L., Bonini N.M. Ataxin-3 suppresses polyglutamine neurodegeneration in Drosophila by a ubiquitin-associated mechanisms. Mol. Cell 2005, 18:37-48.
81. Kaytor M.D., Wilkinson K.D., Warren S.T. Modulating huntingtin half-life alters polyglutamine-dependent aggregate formation and cell toxicity. J. Neurochem. 2004, 89:962-973.
82. Michalik A., van Broeckhoven C. Proteasome degrades soluble expanded polyglutamine completely and efficiently. Neurobiol. Dis. 2004, 16:202-211.
83. Kim M., Lee H.S., LaForet G., McIntyre C., Martin E.J., Chang P., Kim T.W., Williams M., Reddy P.H., Tagle D., Boyce F.M., Won L., Heller A., Aronin N., DiFiglia M. Mutant huntingtin expression in clonal striatal cells: Dissociation of inclusion formation and neuronal survival by caspase inhibition. J. Neurosci. 1999, 19:964-973.
84. Ravikumar B., Duden R., Rubinsztein D.C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol Genet. 2002, 11:1107-1117.
85. Qin Z.H., Wang Y., Kegel K.B., Kazantsev A., Apostol B.L., Thomspon L.M., Yoder J., Aronin N., DiFiglia M. Autophagy regulates the processing of amino terminal huntingtin fragments. Hum. Mol Genet. 2003, 12:3231-3244.
86. Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O'Kane C.J., Rubinsztein D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 2004, 36:585-595.
87. Gunawardena S., Her L.S., Brusch R.G., Laymon R.A., Niesman I.R., Gordesky-Gold B., Sintasath L., Bonini N.M., Goldstein L.S. Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 2003, 40:25-40.
88. Lee W.C., Yoshihara M., Littleton J.T. Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease. Proc. Natl. Acad. Sci. USA 2004, 101:3224-3229.
89. Ravikumar B., Acevedo-Arozena A., Imarisio S., Berger Z., Vacher C., O'Kane C.J., Brown S.D., Rubinsztein D.C. Dynein mutations impair autophagic clearance of aggregate-prone proteins. Nat. Genet. 2005, 37:771-776.
90. Luthi-Carter R., Strand A., Peters N.L., Solano S.M., Hollingsworth Z.R., Menon A.S., Frey A.S., Spektor B.S., Penney E.B., Schilling G., Ross C.A., Borchelt D.R., Tapscott S.J., Young A.B., Cha J.H., Olson J.M. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum. Mol Genet. 2000, 9:1259-1271.
91. Luthi-Carter R., Hanson S.A., Strand A.D., Bergstrom D.A., Chun W., Peters N.L., Woods A.M., Chan E.Y., Kooperberg C., Krainc D., Young A.B., Tapscott S.J., Olson J.M. 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.
92. Steffan J.S., Kazantsev A., Spasic-Boskovic O., Greewald 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.
93. Nucifora F.C., Sasaki M., Peters M.F., Huang H., Cooper J.K., Yamada M., Takahashi H., Tsuji S., Troncoso J., Dawson V.L., Dawson T.M., Ross C.A. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 2001, 291:2423-2428.
94. Wyttenbach A., Swartz J., Kita H., Thykjaer T., Carmichael J., Bradley J., Brown R., Maxwell M., Schapira A., Orntoft T.F., Kato K., Rubinsztein D.C. 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.
95. Shimohata T., Nakajima T., Yamada M., Uchida C., Onodera O., Naruse S., Kimura T., Koide R., Nozaki K., Sano Y., Ishiguro H., Sakoe K., Ooshima T., Sato A., Ikeuchi T., Oyake M., Sato T., Aoyai Y., Hozumi I., Nagatsu T., Takiyama Y., Nishizawa M., Goto J., Kanzawa I., Davidson I., Tanese N., Takahashi H., Tsuji S. Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nat. Genet. 2000, 26:29-36.
96. Obrietan K., Hoyt K.R. CRE-mediated transcription is increased in Huntington's desease transgenic mice. J. Neurosci. 2004, 24:791-796.
97. Mantamadiotis T., Lemberger T., Bleckmann S.C., Kern H., Kretz O., Martin Villalba A., Tronche F., Kellendonk C., Gau D., Kapfhammer J., Otto C., Schmid W., Schutz G. Disruption of CREB function in brain leads to neurodegeneration. Nat. Genet. 2002, 31:47-54.
98. Steffan J.S., Bodai L., Pallos J., Poelman M., McCampbell A., Apostol B.L., Kazantsev A., Schmidt E., Zhu Y.Z., Greenwald M., Kurokawa R., Housman D.E., Jackson G.R., Marsh J.L., Thompson L.M. Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeration in Drosophila. Nature 2001, 413:739-743.
99. Hockly E., Richon V.M., Woodman B., Smith D.L., Zhou X., Rosa E., Sathasivam K., Ghazi-Noori S., Mahal A., Lowden P.A., Steffan J.S., Marsh J.L., Thompson L.M., Lewis C.M., Marks P.A., Bates G.P. 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.
100. Huang C.C., Faber P.W., Persichetti F., Mittal V., Vonsattel J.P., MacDonald M.E., Gusella J.F. Amyloid formation by mutant huntingtin: Threshold, progressivity and recruitment of normal polyglutamine proteins. Somat. Cell. Mol. Genet. 1998, 24:217-233.
101. Boutell J.M., Thomas P., Neal J.W., Weston V.J., Duce J., Harper P.S., Jones A.L. Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. Hum. Mol Genet. 1999, 8:1647-1655.
102. Dunah A.W., Jeong H., Griffin A., Kim Y.M., Standaert D.G., Hersch S.M., Mouradian M.M., Young A.B., Tanese N., Krainc D. Sp1 and TAFIII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
103. Holbert S., Denghien I., Kiechle T., Rosenblatt A., Wellington C., Hayden M.R., Margolis R.L., Ross C.A., Dausset J., Ferrante R.J., Neri C. 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. USA 2001, 98:1811-1816.
104. Zuccato C., Tartari M., Crotti A., Goffredo D., Valenza M., Conti L., Cataudella T., Leavitt B.R., Hayden M.R., Timmusk T., Rigamonti D., Cattaneo E. Huntingtin interacts with REST/NRSF to modulate the transcription of NRSE-controlled neuronal genes. Nat. Genet. 2003, 35:76-83.
105. Igarashi S., Morita H., Bennett K.M., Tanaka Y., Engelender S., Peters M.F., Cooper J.K., Wood J.D., Sawa A., Ross C.A. Inducible PC12 cell model of Huntington's disease shows toxicity and decreased histone acetylation. Neuro Report 2003, 14:565-568.
106. Trettel F., Rigamonti D., Hilditch-Maguire P., Wheeler V.C., Sharp A.H., Persichetti F., Cattaneo E., MacDonald M.E. Dominant phenotypes produced by the HD mutation in STHdh(Q111) striatal cells. Hum. Mol. Genet. 2000, 9:2799-2809.
107. Hughes R.E., Lo R.S., Davis C., Strand A.D., Neal C.L., Olson J.M., Fields S. Altered transcription in yeast expressing expanded polyglutamine. Proc. Natl. Acad. Sci. USA 2001, 98:13201-13206.
108. Schilling G., Becher M.W., Sharp A.H., Jinnah H.A., Duan K., Kotzuk J.A., Slunt H.H., Ratovitski T., Cooper J.K., Jenkins N.A., Copeland N.G., Price D.L., Ross C.A., Borchelt D.R. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum. Mol. Genet. 1999, 8:397-407.
109. Laforet G.A., Sapp E., Chase K., McIntyre C., Boyce F.M., Campbell M., Cadigan B.A., Warzecki L., Tagle D.A., Reddy P.H., Cepeda C., Calvert C.R., Jokel E.S., Klapstein G.J., Ariano M.A., Levine M.S., DiFiglia M., Aronin N. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J. Neurosci. 2001, 21:9112-9123.
110. Slow E.J., van Raamsdonk J., Rogers D., Coleman S.H., Graham R.K., Deng Y., Oh R., Bissada N., Hossain S.M., Yang Y.Z., Li X.J., Simpson E.M., Gutekunst C.A., Leavitt B.R., Hayden M.R. Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease. Hum. Mol. Genet. 2003, 12:1555-1567.
111. Reddy P.H., Williams M., Charles V., Garrett L., Pike-Buchanan L., Whetsell W.O., Miller G., Tagle D.A. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat. Genet. 1998, 20:198-202.
112. Wheeler V.C., White J.K., Gutekunst C.A., Vrbanac V., Weaver M., Li X.J., Li S.H., Yi H., Vonsattel J.P., Gusella J.F., Hersch S., Auerbach W., Joyner A.L., MacDonald M.E. Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice. Hum. Mol. Genet. 2000, 9:503-513.
113. Levine M.S., Klapstein G.J., Koppel A., Gruen E., Cepeda C., Vargas M.E., Jokel E.S., Carpenter E.M., Zanjani H., Hurst R.S., Efstratiadis A., Zeitlin S., Chesselet M.F. Enhanced sensitivity to N-methyl-d-aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease. J. Neurosci. Res. 1999, 58:515-532.
114. von Horsten S., Schmitt I., Nguyen H.P., Holzmann C., Schmidt T., Walther T., Bader M., Pabst R., Kobbe P., Krotova J., Stiller D., Kask A., Vaarmann A., Rathke-Hartlieb S., Schulz J.B., Grasshoff U., Bauer I., Vieira-Saecker A.M., Paul M., Jones L., Lindenberg K.S., Landwehrmeyer B., Bauer A., Li X.J., Riess O. Transgenic rat model of Huntington's disease. Hum. Mol. Genet. 2003, 12:617-624.
115. de Almeida L.P., Ross C.A., Zala D., Aebischer P., Deglon N. Lentiviral-mediated delivery of mutant huntingtin in the striatum of rats induces a selective neuropathology modulated by polyglutamine repeat size, huntingtin expression levels, and protein length. J. Neurosci. 2002, 22:3473-3483.
116. Hughes R.E., Olson J.M. Therapeutic opportunities in polyglutamine disease. Nat. Med. 2001, 7:419-423.
117. Heiser V., Engemann S., Brocker W., Dunkel I., Boeddrich A., Waelter S., Nordhoff E., Lurz R., Schugardt N., Rautenberg S., Herhaus C., Barnickel G., Bottcher H., Lehrach H., Wanker E.E. Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay. Proc. Natl. Acad. Sci. USA 2002, 99(Suppl. 4):16400-16406.
118. Lipinski C.A., Lombardo F., Dominy B.W., Feeney P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug. Deliv. Rev. 2001, 46:3-26.
119. Aiken C.T., Tobin A.J., Schweitzer E.S. A cell-based screen for drugs to treat Huntington's disease. Neurobiol. Dis. 2004, 16:546-555.
120. Pollitt S.K., Pallos J., Shao J., Desai U.A., Ma A.A., Thompson L.M., Marsh J.L., Diamond M.I. A rapid cellular FRET assay of polyglutamine aggregation identifies a novel inhibitor. Neuron 2003, 40:685-694.
121. Tobin A.J., Signer E.R. Huntington's disease: The challenge for cell biologists. Trends Cell Biol. 2000, 10:531-536.
122. Wang J., Gines S., MacDonald M.E., Gusella J.F. Reversal of a full-length mutant huntingtin neuronal cell phenotype by chemical inhibitors of polyglutamine-mediated aggregation. BMC Neurosci. 2005, 6:1.
123. Wang W., Duan W., Igarashi S., Morita H., Nakamura M., Ross C.A. Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell model. Neurobiol Dis. 2005, 20:500-508.
124. Zhang X., Smith D.L., Meriin A.B., Engemann S., Russel D.E., Roark M., Washington S.L., Maxwell M.M., Marsh J.L., Thompson L.M., Wanker E.E., Young A.B., Housman D.E., Bates G.P., Sherman M.Y., Kazantsev A.G. A potent small molecule inhibits polyglutamine aggregation in Huntington's disease neurons and suppresses neurodegeneration in vivo. Proc. Natl. Acad. Sci. USA 2005, 102:892-897.
125. Meriin A.B., Zhang X., He X., Newnam G.P., Chernoff Y.O., Sherman M.Y. Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J. Cell Biol. 2002, 157:997-1004.
126. Heiser V., Scherzinger E., Boeddrich A., Nordhoff E., Lurz R., Schugardt N., Lehrach H., Wanker E.E. Inhibition of huntingtin fibrillogenesis by specific antibodies and small molecules: Implications for Huntington's disease therapy. Proc. Natl. Acad. Sci. USA 2000, 97:6739-6744.
127. Apostol B.L., Kazantsev A., Raffioni S., Illes K., Pallos J., Bodai L., Slepko N., Bear J.E., Gertler F.B., Hersch S., Housman D.E., Marsh J.L., Thompson L.M. A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila. Proc. Natl. Acad. Sci. USA 2003, 100:5950-5955.
128. Smith D.L., Portier R., Woodman B., Hockly E., Mahal A., Klunk W.E., Li X.J., Wanker E., Murray K.D., Bates G.P. Inhibition of polyglutamine aggregation in R6/2 HD brain slices-complex dose-response profiles. Neurobiol. Dis. 2001, 8:1017-1026.
129. McCampbell A., Taye A.A., Whitty L., Penney E., Steffan J.S., Fischbeck K.H. Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc. Natl. Acad. Sci. USA 2001, 98:15179-15184.
130. 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., Beal M.F. Neuroprotective effects of phenylbutyrate in the N171-82Q transgenic mouse model of Huntington's disease. J. Biol. Chem. 2005, 280:556-563.
131. 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., Hersch S.M. Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice. J. Neurosci. 2003, 23:9418-9427.
132. Parker J.A., Arango M., Abderrahmane S., Lambert E., Tourette C., Catoire H., Neri C. Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons. Nat. Genet. 2005, 37:349-350.
133. Marsh J.L., Pallos J., Thompson L.M. Fly models of Huntington's disease. Hum. Mol. Genet. 2003, 12(Spec. No. 2):R187-R193.
134. Marsh J.L., Thompson L.M. Can flies help humans treat neurodegenerative diseases?. Bioessays 2004, 26:485-496.
135. Agrawal N., Pallos J., Slepko N., Apostol B.L., Bodai L., Chang L.W., Chiang A.S., Thompson L.M., Marsh J.L. Identification of combinatorial drug regimens for treatment of Huntington's disease using Drosophila. Proc. Natl. Acad. Sci. USA 2005, 102:3777-3781.
136. Mahmood I. Allometric issues in drug development. J. Pharm. Sci. 1999, 88:1101-1106.
137. Mahmood I. Prediction of clearance, volume of distribution and half-life by allometric scaling and by use of plasma concentrations predicted from pharmacokinetic constants: A comparative study. J. Pharm. Pharmacol. 1999, 51:905-910.
138. Beal M.F., Brouillet E., Jenkins B.G., Ferrante R.J., Kowall N.W., Miller J.M., Storey E., Srivastava R., Rosen B.R., Hyman B.T. Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid. J. Neurosci. 1993, 13:4181-4192.
139. Beal M.F., Kowall N.W., Ellison D.W., Mazurek M.F., Swartz K.J., Martin J.B. Replication of the neurochemical characteristics of Huntington's disease by quinolinic acid. Nature 1986, 321:168-171.
140. de Lago E., Urbani P., Ramos J.A., Di Marzo V., Fernandez-Ruiz J. Arvanil, a hybrid endocannabinoid and vanilloid compound, behaves as an antihyperkinetic agent in a rat model of Huntington's disease. Brain Res. 2005, 1050:210-216.
141. Kim J.H., Kim S., Yoon I.S., Lee J.H., Jang B.J., Jeong S.M., Lee B.H., Han J.S., Oh S., Kim H.C., Park T.K., Rhim H., Nah S.Y. Protective effects of ginseng saponins on 3-nitropropionic acid-induced striatal degeneration in rats. Neuropharmacology 2005, 48:743-756.
142. Rodriguez A.I., Willing A.E., Saporta S., Cameron D.F., Sanberg P.R. Effects of Sertoli cell transplants in a 3-nitropropionic acid model of early Huntington's disease: A preliminary study. Neurotoxicol. Res. 2003, 5:443-450.
143. McBride J.L., During M.J., Wuu J., Chen E.Y., Leurgans S.E., Kordower J.H. Structural and functional neuroprotection in a rat model of Huntington's disease by viral gene transfer of GDNF. Exp. Neurol. 2003, 181:213-223.
144. Diguet E., Fernagut P.O., Wei X., Du Y., Rouland R., Gross C., Bezard E., Tison F. Deleterious effects of minocycline in animal models of Parkinson's disease and Huntington's disease. Eur. J. Neurosci. 2004, 19:3266-3276.
145. Diguet E., Rouland R., Tison F. Minocycline is not beneficial in a phenotypic mouse model of Huntington's disease. Ann. Neurol. 2003, 54:841-842.
146. Keene C.D., Rodrigues C.M., Eich T., Linehan-Stieers C., Abt A., Kren B.T., Steer C.J., Low W.C. A bile acid protects against motor and cognitive deficits and reduces striatal degeneration in the 3-nitropropionic acid model of Huntington's disease. Exp. Neurol. 2001, 171:351-360.
147. Roitberg B.Z., Emborg M.E., Sramek J.G., Palfi S., Kordower J.H. Behavioral and morphological comparison of two nonhuman primate models of Huntington's disease. Neurosurgery 2002, 50:137-145. discussion 145-136.
148. Kendall A.L., Rayment F.D., Torres E.M., Baker H.F., Ridley R.M., Dunnett S.B. Functional integration of striatal allografts in a primate model of Huntington's disease. Nat. Med. 1998, 4:727-729.
149. Dunnett S.B. Striatal reconstruction by striatal grafts. J. Neural. Transm. Suppl. 1999, 55:115-129.
150. Dunnett S.B., Carter R.J., Watts C., Torres E.M., Mahal A., Mangiarini L., Bates G., Morton A.J. Striatal transplantation in a transgenic mouse model of Huntington's disease. Exp. Neurol. 1998, 154:31-40.
151. Georgiou N., Bradshaw J.L., Chiu E., Tudor A., O'Gorman L., Phillips J.G. Differential clinical and motor control function in a pair of monozygotic twins with Huntington's disease. Mov. Disord. 1999, 14:320-325.
152. Carter R.J., Hunt M.J., Morton A.J. Environmental stimulation increases survival in mice transgenic for exon 1 of the Huntington's disease gene. Mov. Disord. 2000, 15:925-937.
153. Van Dellen A., Hannan A.J. Genetic and environmental factors in the pathogenesis of Huntington's disease. Neurogenetics 2004, 5:9-17.
154. Hockly E., Cordery P.M., Woodman B., Mahal A., van Dellen A., Blakemore C., Lewis C.M., Hannan A.J., Bates G.P. Environmental enrichment slows disease progression in R6/2 Huntington's disease mice. Ann. Neurol. 2002, 51:235-242.
155. Schilling G., Savonenko A.V., Coonfield M.L., Morton J.L., Vorovich E., Gale A., Neslon C., Chan N., Fromholt D., Ross C.A., Borchelt D.R. Environmental, pharmacological, and genetic modulation of the HD phenotype in transgenic mice. Exp. Neurol. 2004, 187:137-149.
156. Van Praag H., Kempermann G., Gage F.H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 1999, 2:266-270.
157. Van Praag H., Christie B.R., Sejnowski T.J., Gage F.H. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc. Natl. Acad. Sci. USA 1999, 96:13427-13431.
158. Brown J., Cooper-Kuhn C.M., Kempermann G., Van Praag H., Winkler J., Gage F.H., Kuhn H.G. Enriched environment and physical activity stimulate hippocampal but not olfactory bulb neurogenesis. Eur. J. Neurosci. 2003, 17:2042-2046.
159. Spires T.L., Grote H.E., Garry S., Cordery P.M., Van Dellen A., Blakemore C., Hannan A.J. Dendritic spine pathology and deficits in experience-dependent dendritic plasticity in R6/1 Huntington's disease transgenic mice. Eur. J. Neurosci. 2004, 19:2799-2807.
160. Spires T.L., Grote H.E., Varshney N.K., Cordery P.M., van Dellen A., Blakemore C., Hannan A.J. Environmental enrichment rescues protein deficits in a mouse model of Huntington's disease, indicating a possible disease mechanism. J. Neurosci. 2004, 24:2270-2276.
161. Glass M., van Dellen A., Blakemore C., Hannan A.J., Faull R.L. Delayed onset of Huntington's disease in mice in an enriched environment correlates with delayed loss of cannabinoid CB1 receptors. Neuroscience 2004, 123:207-212.
162. Tanaka M., Machida Y., Niu S., Ikeda T., Jana N.R., Doi H., Kurosawa M., Nekooki M., Nukina N. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat. Med. 2004, 10:148-154.
163. Smith D.L., Woodman B., Mahal A., Sathasivam K., Ghazi-Noori S., Lowden P.A., Bates G.P., Hockly E. Minocycline and doxycycline are not beneficial in a model of Huntington's disease. Ann. Neurol. 2003, 54:186-196.
164. Chen M., Ona V.O., Li M., Ferrante R.J., Fink K.B., Zhu S., Bian J., Guo L., Farrell L.A., Hersch S.M., Hobbs W., Vonsattel J.P., Cha J.H., Friedlander R.M. Minocycline inhibits caspace-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat. Med. 2000, 6:797-801.
165. Diguet E., Gross C.E., Tison F., Bezard E. Rise and fall of minocycline in neuroprotection: Need to promote publication of negative results. Exp. Neurol. 2004, 189:1-4.
166. Sanchez I., Mahlke C., Yuan J. Pivotal role of oligomerization in expanded polyglutamine neurodegenrative disorders. Nature 2003, 421:373-379.
167. 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., Kristal B.S., Stavrovskaya I.G., Hewett S., Rubinsztein D.C., Langley B., Ratan R.R. Chemotherapy for the brain: The antitumor antibiotic mithramycin prolongs survival in a mouse model of Huntington's disease. J. Neurosci. 2004, 24:10335-10342.
168. Minamiyama M., Katsuno M., Adachi H., Waza M., Sang C., Kobayashi Y., Tanaka F., Doyu M., Inukai A., Sobue G. Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Hum. Mol. Genet. 2004, 13:1183-1192.
169. Schilling G., Coonfield M.L., Ross C.A., Borchelt D.R. Coenzyme Q10 and remacemide hydrochloride amelio-rate motor deficits in a Huntington's disease transgenic mouse model. Neurosci. Lett. 2001, 315:149-153.
170. Ferrante R.J., Andreassen O.A., Dedeoglu A., Ferrante K.L., Jenkins B.G., Hersch S.M., Beal M.f. Therapeutic effects of coenzyme Q10 and remacemide in transgenic mouse models of Huntington's disease. J. Neurosci. 2002, 22:1592-1599.
171. Andreassen O.A., Ferrante R.J., Dedeoglu A., Beal M.F. Lipoic acid improves survival in transgenic mouse models of Huntington's disease. Neuro Report 2001, 12:3371-3373.
172. Klivenyi P, Ferrante R.J., Gardian G., Browne S., Chabrier P.E., Beal M.F. Increased survival and neuroprotective effects of BN82451 in a transgenic mouse model of Huntington's disease. J. Neurochem. 2003, 86:267-272.
173. Chou S.Y., Lee Y.C., Chen H.M., Chiang M.C., Lai H.L., Chang H.H., Wu Y.C., Sun C.N., Chien C.L., Lin Y.S., Wang S.C., Tung Y.Y., Chang C., Chern Y. CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model. J. Neurochem. 2005, 93:310-320.
174. Morton A.J., Hunt M.J., Hodges A.K., Lewis P.D., Redfern A.J., Dunnett S.B., Jones L. A combination drug therapy improves cognition and reverses gene expression changes in a mouse model of Huntigton's disease. Eur J. Neurosci. 2005, 21:855-870.
175. Andreassen O.A., Ferrante R.J., Huang H.M., Dedeoglu A., Park L., Ferrante K.L., Kwon J., Borchelt D.R., Ross C.A., Gibson G.E., Beal M.F. Dichloroacetate exerts therapeutic effects in transgenic mouse models of Huntington's disease. Ann. Neurol. 2001, 50:112-117.
176. Keene C.D., Rodrigues C.M., Eich T., Chhabra M.S., Steer C.J., Low W.C. Tauroursodeoxycholic acid, a bile acid, is neuroprotective in a transgenic animal model of Huntington's disease. Proc. Natl. Acad. Sci. USA 2002, 99:10671-10676.
177. Ona V.O., Li M., Vonsattel J.P., Andrews L.J., Khan S.Q., Chung W.M., Frey A.S., Menon A.S., Li X.J., Stieg P.E., Yuan J., Penney J.B., Young A.B., Cha J.H., Friedlander R.M. Inhibition of caspase-1 slows disease progression in a mouse model of Hungtington's disease. Nature 1999, 399:263-267.
178. Karpuj M.V., Becher M.W., Springer J.E., Chabas D., Youssef S., Pedotti R., Mitchell D., Steinman L. Prolonged survival and decreased abnormal movements in transgenic model of Huntington disease, with administration of the transglutaminase inhibitor cystamine. Nat. Med. 2002, 8:143-149.
179. Dedeoglu A., Kubilus J.K., Yang L., Ferrante K.L., Hersch S.M., Beal M.F., Ferrante R.J. Creatine therapy provides neuroprotection after onset of clinical symptoms in Huntington's disease transgenic mice. J. Neurochem. 2003, 85:1359-1367.
180. Bailey C.D., Johnson G.V. The protective effects of cystamine in the R6/2 Huntington's disease mouse involve mechanisms other than the inhibition of tissue transglutaminase. Neurobiol. Aging 2005, in press.
181. Ferrante R.J., Andreassen O.A., Jenkins B.G., Dedeoglu A., Kuemmerle S., Kubilus J.K., Kaddurah-Daouk R., Hersch S.M., Beal M.F. Neuroprotective effects of creatine in a transgenic mouse model of Huntington's disease. J. Neurosci. 2000, 20:4389-4397.
182. Andreassen O.A., Dedeoglu A., Ferrante R.J., Jenkins B.G., Ferrante K.L., Thomas M., Friedlich A., Browne S.E., Schilling G., Borchelt D.R., Hersch S.M., Ross C.A., Beal M.F. Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease. Neurobiol. Dis. 2001, 8:479-491.
183. Wang X., Sarkar A., Cicchetti F., Yu M., Zhu A., Jokivarsi K., Saint-Pierre M., Brownell A.L. Cerebral PET imaging and histological evidence of transglutaminase inhibitor cystamine induced neuroprotection in transgenic R6/2 mouse model of Huntington's disease. J. Neurol. Sci. 2005, 231:57-66.
184. Bantubungi K., Jacquard C., Greco A., Pintor A., Chtarto A., Tai K., Galas M.C., Tenenbaum L., Deglon N., Popoli P., Minghetti L., Brouillet E., Brotchi J., Levivier M., Minghetti L., Brouillet E., Brotchi J., Levivier M., Schiffmann S.N., Blum D. Minocycline in pheno-typic models of Huntington's disease. Neurobiol. Dis. 2005, 18:206-217.
185. Harper S.Q., Staber P.D., He X., Eliason S.L., Martins I.H., Mao Q., Yang L., Kotin R.M., Paulson H.L., Davidson B.L. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc. Natl. Acad. Sci. USA 2005, 102:5820-5825.
186. Miller T.W., Shirley T.L., Wolfgang W.J., Kang X., Messer A. DNA vaccination against mutant huntingtin amelio-rates the HDR6/2 diabetic phenotype. Mol. Ther. 2003, 7:572-579.
187. Dedeoglu A., Kubilus J.K., Jeitner T.M., Matson S.A., Bogdanov M., Kowall N.W., Matson W.R., Cooper A.J., Ratan R.R., Beal M.F., Hersch S.M., Ferrante R.J. Therapeutic effects of cystamine in a murine model of Huntington's disease. J. Neurosci. 2002, 22:8942-8950.
188. Schiefer J., Landwehrmeyer G.B., Luesse H.G., Sprunken A., Puls C., Milkereit A., Milkereit E., Kosinski C.M. Riluzole prolongs survival time and alters nuclear inclusion formation in a transgenic mouse model of Huntington's disease. Mov. Disord. 2002, 17:748-757.
189. 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.
190. Popovic N., Maingay M., Kirik D., Brundin P. Lentiviral gene delivery of GDNF into the striatum of R6/2 Hungtinton mice fails to attenuate behavioral and neuropathological changes. Exp. Neurol. 2005, 193:65-74.
191. Zucker B., Ludin D.E., Gerds T.A., Lucking C.H., Landwehrmeyer G.B., Feuerstein T.J. Gabapentinlactam, but not gabapentin, reduces protein aggregates and improves motor performance in a transgenic mouse model of Huntington's disease. Naunyn Schmiedeberg's Arch. Pharmacol. 2004, 370:131-139.
192. Schiefer J., Sprunken A., Puls C., Luesse H.G., Milkereit A., Milkereit E., Johann V., Kosinski C.M. The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington's disease. Brain Res. 2004, 1019:246-254.
193. Duan W., Guo Z., Jiang H., Ladenheim B., Xu X., Cadet J.L., Mattson M.P. Paroxetine retards disease onset and progression in huntington mutant mice. Ann. Neurol. 2004, 55:590-594.
194. Clifford J.J., Drago J., Natoli A.L., Wong J.Y., Kinsella A., Waddington J.L., Vaddadi K.S. Essential fatty acids given from conception prevent topographies of motor deficit in a transgenic model of Huntington's disease. Neuroscience 2002, 109:81-88.
195. Van Dellen A., Blakemore C., Deacon R., York D., Hannan A.J. Delaying the onset of Huntington's in mice. Nature 2000, 404:721-722.
196. Duan W., Guo Z., Jiang H, Ware M., Li X.J., Mattson M.P. Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice. Proc. Natl. Acad. Sci. USA 2003, 100:2911-2916.
197. Ende N., Chen R. Human umbilical cord blood cells ameliorate Huntington's disease in transgenic mice. J. Med. 2001, 32:231-240.
198. Morley J.F., Brignull H.R., Weyers J.J., Morimoto R.I. The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 2002, 99:10417-10422.