Pathogenic mechanisms in huntington's disease

International Review of Neurobiology

Volumn 98, Issue , 2011, Pages 373-418

  Jones, Lesley ^a   Hughes, Alis ^a  

^a CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Aggregates; CAG repeat instability; Excitotoxicity; Huntingtin; Huntington's disease; Mouse models; Mutant huntingtin; Pathogenic mechanisms; Protein degradation; Protein processing; Transport

Indexed keywords

BRAIN DERIVED NEUROTROPHIC FACTOR; BRAIN PROTEIN; HUNTINGTIN; HUNTINGTIN ASSOCIATED PROTEIN 1; MESSENGER RNA; MITOGEN ACTIVATED PROTEIN KINASE 10; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 1; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; REMACEMIDE; UNCLASSIFIED DRUG;

AUTOPHAGY; BOOK; CAG REPEAT; CONFORMATIONAL TRANSITION; DOWNSTREAM PROCESSING; ENERGY METABOLISM; EXCITOTOXICITY; GENE; HUMAN; HUNTINGTIN GENE; HUNTINGTON CHOREA; INTRACELLULAR TRANSPORT; MUTATIONAL ANALYSIS; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; PROTEIN AGGREGATION; PROTEIN CLEAVAGE; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROCESSING; PROTEIN TRANSPORT; SUMOYLATION; TRANSCRIPTION REGULATION;

EID: 80052545388     PISSN: 00747742     EISSN: None     Source Type: Book Series    
DOI: 10.1016/B978-0-12-381328-2.00015-8     Document Type: Chapter

References (335)

1. Aiken C.T., Steffan J.S., Guerrero C.M., Khashwji H., Lukacsovich T., Simmons D., Purcell J.M., Menhaji K., Zhu Y.Z., Green K., Laferla F., Huang L., Thompson L.M., Marsh J.L. Phosphorylation of threonine 3: implications for Huntingtin aggregation and neurotoxicity. J. Biol. Chem. 2009, 284:29427-29436.
2. Albin R.L., Young A.B., Penney J.B., Handelin B., Balfour R., Anderson K.D., Markel D.S., Tourtellotte W.W., Reiner A. Abnormalities of striatal projection neurons and N-methyl-D-aspartate receptors in presymptomatic Huntington's disease. N. Engl. J. Med. 1990, 322:1293-1298.
3. Ali N.J., Levine M.S. Changes in expression of N-methyl-D-aspartate receptor subunits occur early in the R6/2 mouse model of Huntington's disease. Dev. Neurosci. 2006, 28:230-238.
4. Appella E., Anderson C.W. Post-translational modifications and activation of p53 by genotoxic stresses. Eur. J. Biochem. 2001, 268:2764-2772.
5. Arenas J., Campos Y., Ribacoba R., Martin M.A., Rubio J.C., Ablanedo P., Cabello A. Complex I defect in muscle from patients with Huntington's disease. Ann. Neurol. 1998, 43:397-400.
6. Aronin N., Chase K., Young C., Sapp E., Schwarz C., Matta N., Kornreich R., Lanwehrmeyer B., Bird E., Beal M.F., Vonsattel J.-P., Smith T., Carraway R., Boyce F.M., Young A.B., Penney J.B., DiFiglia M. CAG expansion affects the expression of mutant huntingtin in the Huntington's disease brain. Neuron 1995, 15:1193-1201.
7. 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.
8. Arzberger T., Krampfl K., Leimgruber S., Weindl A. Changes of NMDA receptor subunit (NR1, NR2B) and glutamate transporter (GLT1) mRNA expression in Huntington's disease-an in situ hybridization study. J. Neuropathol. Exp. Neurol. 1997, 56:440-454.
9. Atwal R.S., Truant R. A stress sensitive ER membrane-association domain in Huntingtin protein defines a potential role for Huntingtin in the regulation of autophagy. Autophagy 2008, 4:91-93.
10. Atwal R.S., Xia J., Pinchev D., Taylor J., Epand R.M., Truant R. Huntingtin has a membrane association signal that can modulate huntingtin aggregation, nuclear entry and toxicity. Hum. Mol. Genet. 2007, 16:2600-2615.
11. Auerbach W., Hurlbert M.S., Hilditch-Maguire P., Wadghiri Y.Z., Wheeler V.C., Cohen S.I., Joyner A.L., MacDonald M.E., Turnbull D.H. The HD mutation causes progressive lethal neurological disease in mice expressing reduced levels of huntingtin. Hum. Mol. Genet. 2001, 10:2515-2523.
12. Augood S.J., Faull R.L., Emson P.C. Dopamine D1 and D2 receptor gene expression in the striatum in Huntington's disease. Ann. Neurol. 1997, 42:215-221.
13. Augood S.J., Faull R.L., Love D.R., Emson P.C. Reduction in enkephalin and substance P messenger RNA in the striatum of early grade Huntington's disease: a detailed cellular in situ hybridization study. Neuroscience 1996, 72:1023-1036.
14. Backues S.K., Klionsky D.J. Autophagy Gets in on the Regulatory Act. J. Mol. Cell. Biol. 2010.
15. Bae B.I., Xu H., Igarashi S., Fujimuro M., Agrawal N., Taya Y., Hayward S.D., Moran T.H., Montell C., Ross C.A., Snyder S.H., Sawa A. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005, 47:29-41.
16. Bates G., Harper P.S., Jones L. Huntington's Disease 2002, OUP, Oxford, UK. 3rd.
17. Bauer P.O., Goswami A., Wong H.K., Okuno M., Kurosawa M., Yamada M., Miyazaki H., Matsumoto G., Kino Y., Nagai Y., Nukina N. Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nat. Biotechnol. 2010, 28:256-263.
18. Beal M.F., Ferrante R.J. Experimental therapeutics in transgenic mouse models of Huntington's disease. Nat. Rev. Neurosci. 2004, 5:373-384.
19. Becher M.W., Kotzuk J.A., Sharp A.H., Davies S.W., Bates G.P., Price D.L., Ross C.A. Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol. Dis. 1998, 4:387-397.
20. Bence N.F., Sampat R.M., Kopito R.R. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001, 292:1552-1555.
21. Benn C.L., Landles C., Li H., Strand A.D., Woodman B., Sathasivam K., Li S.H., Ghazi-Noori S., Hockly E., Faruque S.M., Cha J.H., Sharpe P.T., Olson J.M., Li X.J., Bates G.P. Contribution of nuclear and extranuclear polyglutamine to neurological phenotypes in mouse models of Huntington's disease. Hum. Mol. Genet. 2005, 14:3065-3078.
22. 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. Molecular Cell. 2005, 17:351-365.
23. Bennett E.J., Shaler T.A., Woodman B., Ryu K.-Y., Zaitseva T.S., Becker C.H., Bates G.P., Schulman H., Kopito R.R. Global changes to the ubiquitin system in Huntington's disease. Nature 2007, 448:704-708.
24. Bett J.S., Goellner G.M., Woodman B., Pratt G., Rechsteiner M., Bates G.P. Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington's disease mice: exclusion of proteasome activator REGgamma as a therapeutic target. Hum. Mol. Gen. 2006, 15:33-44.
25. Borovecki F., Lovrecic L., Zhou J., Jeong H., Then F., Rosas H.D., Hersch S.M., Hogarth P., Bouzou B., Jensen R.V., Krainc D. Genome-wide expression profiling of human blood reveals biomarkers for Huntington's disease. Proc. Natl. Acad. Sci. USA 2005, 102:11023-11028.
26. Boudreau R.L., McBride J.L., Martins I., Shen S., Xing Y., Carter B.J., Davidson B.L. Nonallele-specific silencing of mutant and wild-type Huntingtin demonstrates therapeutic efficacy in Huntington's disease mice. Mol. Ther. 2009, 17:1053-1063.
27. 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.
28. 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 nuclear inclusion formation. Hum. Mol. Gen. 2005, 14:679-691.
29. Browne S.E. Mitochondria and Huntington's disease pathogenesis: insight from genetic and chemical models. Ann. NY Acad. Sci. 2008, 1147:358-382.
30. Cannella M., Maglione V., Martino T., Ragona G., Frati L., Li G.-M., Squitieri F. DNA instability in replicating Huntington's disease lymphoblasts. BMC Med. Gen. 2009, 10:11.
31. Carmichael J., Chatellier J., Woolfson A., Milstein C., Fersht A.R., Rubinsztein D.C. Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington's disease. Proc. Nat.l. Acad. Sci. USA 2000, 97:9701-9705.
32. Caughey B., Lansbury P.T. Protofibrils, pores, fibrils, and neurodegeneration: separating the responsible protein aggregates from the innocent bystanders. Ann. Rev. Neurosci. 2003, 26:267-298.
33. Caviston J.P., Holzbaur E.L. Huntingtin as an essential integrator of intracellular vesicular trafficking. Trends Cell Biol. 2009, 19:147-155.
34. Cepeda C., Ariano M.A., Calvert C.R., Flores-Hernandez J., Chandler S.H., Leavitt B.R., Hayden M.R., Levine M.S. NMDA receptor function in mouse models of Huntington disease. J. Neurosci. Res. 2001, 66:525-539.
35. Cepeda C., Wu N., Andre V.M., Cummings D.M., Levine M.S. The corticostriatal pathway in Huntington's disease. Progr. Neurobiol. 2007, 81:253-271.
36. Cha J-H.J. Transcriptional signatures in Huntington's disease. Prog. Neurobiol. 2007, 83:228-248.
37. Chai Y., Koppenhafer S.L., Shoesmith S.J., Perez M.K., Paulson H.L. Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum.Mol. Genet. 1999, 8:673-682.
38. Chan E.Y.W., Luthi-Carter R., Strand A., Solano S.M., Hanson S.A., DeJohn M.M., Kooperberg C., Chase K.O., DiFiglia M., Young A.B., Leavitt B.R., Cha J-HJ, Aronin N., Hayden M.R., Olson J.M. Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease. Hum. Mol. Genet. 2002, 11:1939-1951.
39. Chandra S., Shao J., Li J.X., Li M., Longo F.M., Diamond M.I. A common motif targets huntingtin and the androgen receptor to the proteasome. J. Biol. Chem. 2008, 283:23950-23955.
40. Chang D.T., Rintoul G.L., Pandipati S., Reynolds I.J. Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol. Dis. 2006, 22:388-400.
41. Chaturvedi R.K., Adhihetty P., Shukla S., Hennessy T., Calingasan N., Yang L., Starkov A., Kiaei M., Cannella M., Sassone J. Impaired PGC-1alpha function in muscle in Huntington's disease. Hum. Mol. Genet. 2009, 18:3048-3065.
42. Che H.V., Metzger S., Portal E., Deyle C., Riess O., Nguyen H. Localization of sequence variations in PGC-1alpha influence their modifying effect in Huntington disease. Mol. Neurodeg. 2011, 6:1.
43. Chen N., Luo T., Wellington C., Metzler M., McCutcheon K., Hayden M.R., Raymond L.A. Subtype-specific enhancement of NMDA receptor currents by mutant huntingtin. J. Neurochem. 1999, 72:1890-1898.
44. Choo Y.S., Johnson G.V.W., MacDonald M., Detloff P.J., Lesort M. Mutant huntingtin directly increases susceptibility of mitochondria to the calcium-induced permeability transition and cytochrome c release. Hum. Mol. Genet. 2004, 13:1407-1420.
45. Clarke C.E., Lowry M., Quarrell O.W. No change in striatal glutamate in Huntington's disease measured by proton magnetic resonance spectroscopy. Parkinsonism Relat. Disord. 1998, 4:123-127.
46. Colby D.W., Cassady J.P., Lin G.C., Ingram V.M., Wittrup K.D. Stochastic kinetics of intracellular huntingtin aggregate formation. Nat. Chem. Biol. 2006, 2:319-323.
47. Colby D.W., Chu Y., Cassady J.P., Duennwald M., Zazulak H., Webster J.M., Messer A., Lindquist S., Ingram V.M., Wittrup K.D. Potent inhibition of huntingtin aggregation and cytotoxicity by a disulfide bond-free single-domain intracellular antibody. Proc. Natl. Acad. Sci.USA 2004, 101:17616-17621.
48. Colin E., Zala D., Liot G., Rangone H., Borrell-Pages M., Li X.J., Saudou F., Humbert S. Huntingtin phosphorylation acts as a molecular switch for anterograde/retrograde transport in neurons. EMBO J. 2008, 27:2124-2134.
49. Cooper D.N., Ball E.V., Krawczak M. The human gene mutation database. Nucleic Acids Res. 1998, 26:285-287.
50. Coyle J.T., Schwarcz R. Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature 1976, 263:244-246.
51. 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.
52. Dahlgren P.R., Karymov M.A., Bankston J., Holden T., Thumfort P., Ingram V.M., Lyubchenko Y.L. Atomic force microscopy analysis of the Huntington protein nanofibril formation. Nanomedicine 2005, 1:52-57.
53. Davidson B.L., Boudreau R.L. RNA interference: a tool for querying nervous system function and an emerging therapy. Neuron 2007, 53:781-788.
54. 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.
55. Davies S.W., Turmaine M., Cozens B.A., Raza A.S., Mahal A., Mangiarini L., Bates G.P. From neuronal inclusions to neurodegeneration: neuropathological investigation of a transgenic mouse model of Huntington's disease. Philos. Transact. Royal Soc. London Series B, Biol.Sci. 1999, 354:981-989.
56. de Pril R., Fischer D.F., Maat-Schieman M.L., Hobo B., de Vos R.A., Brunt E.R., Hol E.M., Roos R.A., van Leeuwen F.W. Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases. Hum. Mol. Gen. 2004, 13:1803-1813.
57. de Pril R., Hobo B., van Tijn P., Roos R.A., van Leeuwen F.W., Fischer D.F. Modest proteasomal inhibition by aberrant ubiquitin exacerbates aggregate formation in a Huntington disease mouse model. Mol. Cell. Neurosci. 2010, 43:281-286.
58. Deschepper M., Hoogendoorn B., Brooks S., Dunnett S.B., Jones L. Proteomic changes in the brains of Huntington's disease mouse models reflect pathology and implicate mitochondrial changes. Brain Res. Bull. 2011.
59. 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.: Official J. Soci. Neurosci. 2003, 23:11653-11661.
60. DiFiglia M., Sapp E., Chase K., Schwarz C., Meloni A., Young C., Martin E., Vonsattel J.P., Carraway R., Reeves S.A. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 1995, 14:1075-1081.
61. 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.
62. DiFiglia M., Sena-Esteves M., Chase K., Sapp E., Pfister E., Sass M., Yoder J., Reeves P., Pandey R.K., Rajeev K.G., Manoharan M., Sah D.W.Y., Zamore P.D., Aronin N. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. Proc Natl. Acad. Sci. 2007, 104:17204-17209.
63. Ding Q., Lewis J.J., Strum K.M., Dimayuga E., Bruce-Keller A.J., Dunn J.C., Keller J.N. Polyglutamine expansion, protein aggregation, proteasome activity, and neural survival. J. Biol. Chem. 2002, 277:13935-13942.
64. Djousse L., Knowlton B., Cupples L.A., Marder K., Shoulson I., Myers R.H. Weight loss in early stage of Huntington's disease. Neurology 2002, 59:1325-1330.
65. Dragileva E., Hendricks A., Teed A., Gillis T., Lopez E.T., Friedberg E.C., Kucherlapati R., Edelmann W., Lunetta K.L., MacDonald M.E., Wheeler V.C. Intergenerational and striatal CAG repeat instability in Huntington's disease knock-in mice involve different DNA repair genes. Neurobiol. Dis. 2009, 33:37-47.
66. Drouet V., Perrin V., Hassig R., Dufour N., Auregan G., Alves S., Bonvento G., Brouillet E., Luthi-Carter R., Hantraye P., Déglon N. Sustained effects of nonallele-specific Huntingtin silencing. Ann. Neurol. 2009, 65:276-285.
67. Duennwald M.L., Lindquist S. Impaired ERAD and ER stress are early and specific events in polyglutamine toxicity. Genes Dev. 2008, 22:3308-3319.
68. 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 TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
69. Ehrnhoefer D.E., Duennwald M., Markovic P., Wacker J.L., Engemann S., Roark M., Legleiter J., Marsh J.L., Thompson L.M., Lindquist S., Muchowski P.J., Wanker E.E. Green tea (-)-epigallocatechin-gallate modulates early events in huntingtin misfolding and reduces toxicity in Huntington's disease models. Hum. Mol. Gen. 2006, 15:2743-2751.
70. Estrada Sanchez A.M., Mejia-Toiber J., Massieu L. Excitotoxic neuronal death and the pathogenesis of Huntington's disease. Arch. Med. Res. 2008, 39:265-276.
71. 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.
72. Falush D., Almqvist E.W., Brinkmann R.R., Iwasa Y., Hayden M.R. Measurement of mutational flow implies both a high new-mutation rate for Huntington disease and substantial underascertainment of late-onset cases. Am. J. Hum. Gen. 2001, 68:373-385.
73. Fan M.M., Raymond L.A. N-methyl-D-aspartate (NMDA) receptor function and excitotoxicity in Huntington's disease. Prog. Neurobiol. 2007, 81:272-293.
74. Ferrante R.J. Mouse models of Huntington's disease and methodological considerations for therapeutic trials. Biochimica Biophys. Acta 2009, 1792:506-520.
75. 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.
76. Gafni J., Ellerby L.M. Calpain activation in Huntington's disease. J. Neurosci.: Official J. Soc. Neurosci. 2002, 22:4842-4849.
77. 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.
78. Garcia-Martinez J.M., Perez-Navarro E., Xifro X., Canals J.M., Diaz-Hernandez M., Trioulier Y., Brouillet E., Lucas J.J., Alberch J. BH3-only proteins Bid and Bim(EL) are differentially involved in neuronal dysfunction in mouse models of Huntington's disease. J. Neurosci. Res. 2007, 85:2756-2769.
79. 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.
80. Gines S., Seong I.S., Fossale E., Ivanova E., Trettel F., Gusella J.F., Wheeler V.C., Persichetti F., MacDonald M.E. Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice. Hum. Mol. Genet. 2003, 12:497-508.
81. Giorgini F., Möller T., Kwan W., Zwilling D., Wacker J.L., Hong S., Tsai L.C., Cheah C.S., Schwarcz R., Guidetti P., Muchowski P.J. Histone deacetylase inhibition modulates kynurenine pathway activation in yeast, microglia, and mice expressing a mutant huntingtin fragment. J Biol Chem 2008, 283(12):7390-7400.
82. Giorgini F., Guidetti P., Nguyen Q., Bennett S.C., Muchowski P.J. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat Genet 2005, 37(5):526-531.
83. Goffredo D., Rigamonti D., Tartari M., De Micheli A., Verderio C., Matteoli M., Zuccato C., Cattaneo E. Calcium-dependent cleavage of endogenous wild-type huntingtin in primary cortical neurons. J. Biol. Chem. 2002, 277:39594-39598.
84. Gonitel R., Moffitt H., Sathasivam K., Woodman B., Detloff P.J., Faull R.L., Bates G.P. DNA instability in postmitotic neurons. Proc. Natl. Acad. Sci. USA 2008, 105:3467-3472.
85. Goula A.V., Berquist B.R., Wilson D.M., Wheeler V.C., Trottier Y., Merienne K. Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice. PLoS Gen. 2009, 5:e1000749.
86. Gourfinkel-An I., Cancel G., Duyckaerts C., Faucheux B., Hauw J.J., Trottier Y., Brice A., Agid Y., Hirsch E.C. Neuronal distribution of intranuclear inclusions in Huntington's disease with adult onset. Neuroreport 1998, 9:1823-1826.
87. Graham R.K., Deng Y., Slow E.J., Haigh B., Bissada N., Lu G., Pearson J., Shehadeh J., Bertram L., Murphy Z., Warby S.C., Doty C.N., Roy S., Wellington C.L., Leavitt B.R., Raymond L.A., Nicholson D.W., Hayden M.R. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 2006, 125:1179-1191.
88. Gray M., Shirasaki D.I., Cepeda C., Andre V.M., Wilburn B., Lu X.H., Tao J., Yamazaki I., Li S.H., Sun Y.E., Li X.J., Levine M.S., Yang X.W. Full-length human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. Journal Neurosci.: Official J. Soc. Neurosci. 2008, 28:6182-6195.
89. Gu X., Greiner E.R., Mishra R., Kodali R., Osmand A., Finkbeiner S., Steffan J.S., Thompson L.M., Wetzel R., Yang X.W. Serines 13 and 16 are critical determinants of full-length human mutant huntingtin induced disease pathogenesis in HD mice. Neuron 2009, 64:828-840.
90. Guidetti P., Bates G.P., Graham R.K., Hayden M.R., Leavitt B.R., MacDonald M.E., Slow E.J., Wheeler V.C., Woodman B., Schwarcz R. Elevated brain 3-hydroxykynurenine and quinolinate levels in Huntington disease mice. Neurobiol. Dis. 2006, 23(1):190-197.
91. Guidetti P., Charles V., Chen E.Y., Reddy P.H., Kordower J.H., Whetsell W.O., Schwarcz R., Tagle D.A. Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production. Exp. Neurol. 2001, 169:340-350.
92. Guidetti P., Luthi-Carter R.E., Augood S.J., Schwarcz R. Neostriatal and cortical quinolinate levels are increased in early grade Huntington's disease. Neurobiol. Dis. 2004, 17(3):455-461.
93. 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 polyglutamine proteins in Drosophila. Neuron 2003, 40:25-40.
94. Gutekunst C.A., Levey A.I., Heilman C.J., Whaley W.L., Yi H., Nash N.R., Rees H.D., Madden J.J., Hersch S.M. Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. Proc. Natl. Acad. Sci. USA 1995, 92:8710-8714.
95. Gutekunst C.A., Li S.H., Yi H., Mulroy J.S., Kuemmerle S., Jones R., Rye D., Ferrante R.J., Hersch S.M., Li X.J. Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J. Neurosci. J1 - Jnsci J2 - JN 1999, 19:2522-2534.
96. 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.
97. Hailey D.W., Rambold A.S., Satpute-Krishnan P., Mitra K., Sougrat R., Kim P.K., Lippincott-Schwartz J. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010, 141:656-667.
98. Hansson O., Petersen A., Leist M., Nicotera P., Castilho R.F., Brundin P. Transgenic mice expressing a Huntington's disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity. Proc. Natl. Acad. Sci. USA 1999, 96:8727-8732.
99. Hara T., Nakamura K., Matsui M., Yamamoto A., Nakahara Y., Suzuki-Migishima R., Yokoyama M., Mishima K., Saito I., Okano H., Mizushima N. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006, 441:885-889.
100. Harper S.Q. Progress and challenges in RNA interference therapy for Huntington disease. Arch. Neurol. 2009, 66:933-938.
101. 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.
102. Hayashi-Nishino M., Fujita N., Noda T., Yamaguchi A., Yoshimori T., Yamamoto A. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nature Cell Biol. 2009, 11:1433-1437.
103. Heng M.Y., Duong D.K., Albin R.L., Tallaksen-Greene S.J., Hunter J.M., Lesort M.J., Osmand A., Paulson H.L., Detloff P.J. Early autophagic response in a novel knock-in model of Huntington disease. Hum. Mol. Gen. 2010, 19:3702-3720.
104. Her L.S., Goldstein L.S. Enhanced sensitivity of striatal neurons to axonal transport defects induced by mutant huntingtin. J. Neurosci: Official J. Soc. Neurosci. 2008, 28:13662-13672.
105. Hermel E., Gafni J., Propp S.S., Leavitt B.R., Wellington C.L., Young J.E., Hackam A.S., Logvinova A.V., Peel A.L., Chen S.F., Hook V., Singaraja R., Krajewski S., Goldsmith P.C., Ellerby H.M., Hayden M.R., Bredesen D.E., Ellerby L.M. Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease. Cell Death Differ. 2004, 11:424-438.
106. Ho L.W., Brown R., Maxwell M., Wyttenbach A., Rubinsztein D.C. Wild type Huntingtin reduces the cellular toxicity of mutant Huntingtin in mammalian cell models of Huntington's disease. J. Med. Gen. 2001, 38:450-452.
107. Hochstrasser M. Ubiquitin-dependent protein degradation. Annu. Rev. Genet. 1996, 30:405-439.
108. 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.
109. Hodges A., Strand A.D., Aragaki A.K., Kuhn A., Sengstag T., Hughes G., Elliston L.A., Hartog C., Goldstein D.R., Thu D., Hollingsworth Z.R., Collin F., Synek B., Holmans P.A., Young A.B., Wexler N.S., Delorenzi M., Kooperberg C., Augood S.J., Faull R.L., Olson J.M., Jones L., Luthi-Carter R. Regional and cellular gene expression changes in human Huntington's disease brain. Hum. Mol. Genet. 2006, 15:965-977.
110. Hodges A., Hughes G., Brooks S., Elliston L., Holmans P., Dunnett S.B., Jones L. Brain gene expression correlates with changes in behavior in the R6/1 mouse model of Huntington's disease. Genes Brain Behav. 2008, 7:288-299.
111. Hodgson J.G., Agopyan N., Gutekunst C.A., Leavitt B.R., LePiane F., Singaraja R., Smith D.J., Bissada N., McCutcheon K., Nasir J., Jamot L., Li X.J., Stevens M.E., Rosemond E., Roder J.C., Phillips A.G., Rubin E.M., Hersch S.M., Hayden M.R. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999, 23:181-192.
112. Hoffner G., Kahlem P., Djian P. Perinuclear localization of huntingtin as a consequence of its binding to microtubules through an interaction with beta-tubulin: relevance to Huntington's disease. J. Cell Sci. 2002, 115:941-948.
113. 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.
114. Humbert S., Bryson E.A., Cordelieres F.P., Connors N.C., Datta S.R., Finkbeiner S., Greenberg M.E., Saudou F. The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt. Dev. Cell. 2002, 2:831-837.
115. Hunter J.M., Lesort M., Johnson G.V. Ubiquitin-proteasome system alterations in a striatal cell model of Huntington's disease. J. Neurosci. Res. 2007, 85:1774-1788.
116. Hunter T. The age of crosstalk: phosphorylation, ubiquitination, and beyond. Mol. Cell 2007, 28:730-738.
117. A randomized, placebo-controlled trial of coenzyme Q10 and remacemide in Huntington's disease. Neurology 2001, 57:397-404. Huntington Study Group.
118. 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.
119. 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. Neuroreport 2003, 14:565-568.
120. Ishiguro H., Yamada K., Sawada H., Nishii K., Ichino N., Sawada M., Kurosawa Y., Matsushita N., Kobayashi K., Goto J., Hashida H., Masuda N., Kanazawa I., Nagatsu T. Age-dependent and tissue-specific CAG repeat instability occurs in mouse knock-in for a mutant Huntington's disease gene. J. Neurosci. Res. 2001, 65(4):289-297.
121. 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.
122. Jenkins B.G., Koroshetz W.J., Beal M.F., Rosen B.R. Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy. Neurology 1993, 43:2689-2695.
123. Jeong H., Then F., Melia T.J., Mazzulli J.R., Cui L., Savas J.N., Voisine C., Paganetti P., Tanese N., Hart A.C., Yamamoto A., Krainc D. Acetylation targets mutant huntingtin to autophagosomes for degradation. Cell 2009, 137:60-72.
124. Kahlem P., Djian P. The expanded CAG repeat associated with juvenile Huntington disease shows a common origin of most or all neurons and glia in human cerebrum. Neurosci. Lett. 2000, 286:203-207.
125. Kalchman M.A., Graham R.K., Xia G., Koide H.B., Hodgson J.G., Graham K.C., Goldberg Y.P., Gietz R.D., Pickart C.M., Hayden M.R. Huntingtin is ubiquitinated and interacts with a specific ubiquitin- conjugating enzyme. J. Biol. Chem. 1996, 271:19385-19394.
126. Kalchman M.A., Koide H.B., McCutcheon K., Graham R.K., Nichol K., Nishiyama K., Kazemi-Esfarjani P., Lynn F.C., Wellington C., Metzler M., Goldberg Y.P., Kanazawa I., Gietz R.D., Hayden M.R. HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat. Genet. 1997, 16(1):44-53.
127. Kaltenbach L.S., Romero E., Becklin R.R., Chettier R., Bell R., Phansalkar A., Strand A., Torcassi C., Savage J., Hurlburt A., Cha G.H., Ukani L., Chepanoske C.L., Zhen Y., Sahasrabudhe S., Olson J., Kurschner C., Ellerby L.M., Peltier J.M., Botas J., Hughes R.E. Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration. PLoS Genet. 2007, 3:e82.
128. 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.
129. Kegel K.B., Kim M., Sapp E., McIntyre C., Castano J.G., Aronin N., DiFiglia M. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J. Neurosci. J1 - Jnsci J2 - JN 2000, 20:7268-7278.
130. Kegel K.B., Meloni A.R., Yi Y., Kim Y.J., Doyle E., Cuiffo B.G., Sapp E., Wang Y., Qin Z.H., Chen J.D., Nevins J.R., Aronin N., DiFiglia M. Huntingtin is present in the nucleus, interacts with the transcriptional corepressor C-terminal binding protein, and represses transcription. J. Biol. Chem. 2002, 277:7466-7476.
131. 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(24):3359-3367.
132. Kennedy L., Shelbourne P.F. Dramatic mutation instability in HD mouse striatum: does polyglutamine load contribute to cell-specific vulnerability in Huntington's disease?. Hum. Mol. Genet. 2000, 9(17):2539-2544.
133. 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. J1 - Jnsci J2 - JN 1999, 19:964-973.
134. 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.
135. Kita H., Carmichael J., Swartz J., Muro S., Wyttenbach A., Matsubara K., Rubinsztein D.C., Kato K. Modulation of polyglutamine-induced cell death by genes identified by expression profiling. Hum. Mol. Genet. 2002, 11:2279-2287.
136. Klionsky D.J., Emr S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290:1717-1721.
137. Komatsu M., Waguri S., Chiba T., Murata S., Iwata J., Tanida I., Ueno T., Koike M., Uchiyama Y., Kominami E., Tanaka K. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006, 441:880-884.
138. Kong P.J., Kil M.O., Lee H., Kim S.S., Johnson G.V., Chun W. Increased expression of Bim contributes to the potentiation of serum deprivation-induced apoptotic cell death in Huntington's disease knock-in striatal cell line. Neurol. Res. 2009, 31:77-83.
139. Korolchuk V.I., Menzies F.M., Rubinsztein D.C. Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems. FEBS Lett. 2010, 584:1393-1398.
140. 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.
141. Kovtun I.V., McMurray C.T. Trinucleotide expansion in haploid germ cells by gap repair. Nat. Genet. 2001, 27:407-411.
142. Kuemmerle S., Gutekunst C.A., Klein A.M., Li X.J., Li S.H., Beal M.F., Hersch S.M., Ferrante R.J. Huntington aggregates may not predict neuronal death in Huntington's disease. Ann. Neurol. 1999, 46:842-849.
143. Kuhn A., Goldstein D.R., Hodges A., Strand A.D., Sengstag T., Kooperberg C., Becanovic K., Pouladi M.A., Sathasivam K., Cha J.H., Hannan A.J., Hayden M.R., Leavitt B.R., Dunnett S.B., Ferrante R.J., Albin R., Shelbourne P., Delorenzi M., Augood S.J., Faull R.L., Olson J.M., Bates G.P., Jones L., Luthi-Carter R. Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage. Hum. Mol. Genet. 2007, 16:1845-1861.
144. Kuwert T., Lange H.W., Boecker H., Titz H., Herzog H., Aulich A., Wang B.C., Nayak U., Feinendegen L.E. Striatal glucose consumption in chorea-free subjects at risk of Huntington's disease. J. Neurol. 1993, 241:31-36.
145. Kuwert T., Lange H.W., Langen K.J., Herzog H., Aulich A., Feinendegen L.E. Cortical and subcortical glucose consumption measured by PET in patients with Huntington's disease. Brain: J. Neurol. 1990, 113(Pt 5):1405-1423.
146. 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.: Official J. Soc. Neurosci. 2001, 21:9112-9123.
147. Lakhani V.V., Ding F., Dokholyan N.V. Polyglutamine induced misfolding of huntingtin exon1 is modulated by the flanking sequences. PLoS Comput. Biol. 2010, 6:e1000772.
148. Landles C., Sathasivam K., Weiss A., Woodman B., Moffitt H., Finkbeiner S., Sun B., Gafni J., Ellerby L.M., Trottier Y., Richards W.G., Osmand A., Paganetti P., Bates G.P. Proteolysis of mutant huntingtin produces an exon 1 fragment that accumulates as an aggregated protein in neuronal nuclei in Huntington disease. J Biol Chem 2010, 285(12):8808-8823.
149. Langbehn D.R., Brinkman R.R., Falush D., Paulsen J.S., Hayden M.R. A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length. Clin. Genet. 2004, 65:267-277.
150. Langbehn D.R., Hayden M.R., Paulsen J.S. CAG-repeat length and the age of onset in Huntington disease (HD): a review and validation study of statistical approaches. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010, 153B:397-408.
151. Lee J.M., Ivanova E.V., Seong I.S., Cashorali T., Kohane I., Gusella J.F., MacDonald M.E. Unbiased gene expression analysis implicates the huntingtin polyglutamine tract in extra-mitochondrial energy metabolism. PLoS Gen. 2007, 3:e135.
152. 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.
153. Leon R., Bhagavatula N., Ulukpo O., McCollum M., Wei J. BimEL as a possible molecular link between proteasome dysfunction and cell death induced by mutant huntingtin. Eur. J Neurosci. 2010, 31:1915-1925.
154. Leone T.C., Lehman J.J., Finck B.N., Schaeffer P.J., Wende A.R., Boudina S., Courtois M., Wozniak D.F., Sambandam N., Bernal-Mizrachi C., Chen Z., Holloszy J.O., Medeiros D.M., Schmidt R.E., Saffitz J.E., Abel E.D., Semenkovich C.F., Kelly D.P. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol. 2005, 3:e101.
155. 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.
156. Li H., Li S.H., Yu Z.X., Shelbourne P., Li X.J. Huntingtin aggregate-associated axonal degeneration is an early pathological event in Huntington's disease mice. J. Neurosci. 2001, 21(21):8473-8481.
157. Li H., Wyman T., Yu Z.X., Li S.H., Li X.J. Abnormal association of mutant huntingtin with synaptic vesicles inhibits glutamate release. Hum. Mol. Gen. 2003, 12:2021-2030.
158. Li L., Fan M., Icton C.D., Chen N., Leavitt B.R., Hayden M.R., Murphy T.H., Raymond L.A. Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease. Neurobiol. Aging 2003, 24:1113-1121.
159. Li L., Murphy T.H., Hayden M.R., Raymond L.A. Enhanced striatal NR2B-containing N-methyl-D-aspartate receptor-mediated synaptic currents in a mouse model of Huntington disease. J. Neurophysiol. 2004, 92:2738-2746.
160. Li W., Serpell L.C., Carter W.J., Rubinsztein D.C., Huntington J.A. Expression and characterization of full-length human huntingtin, an elongated HEAT repeat protein. J. Biol. Chem. 2006, 281:15916-15922.
161. Li X.J., Li S.H., Sharp A.H., Nucifora F.C., Schilling G., Lanahan A., Worley P., Snyder S.H., Ross C.A. A huntingtin-associated protein enriched in brain with implications for pathology. Nature 1995, 378(6555):398-402.
162. 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. Mol. Genet. 2001, 10:137-144.
163. Lin J., Wu H., Tarr P.T., Zhang C.Y., Wu Z., Boss O., Michael L.F., Puigserver P., Isotani E., Olson E.N., Lowell B.B., Bassel-Duby R., Spiegelman B.M. Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 2002, 418:797-801.
164. Lloret A., Dragileva E., Teed A., Espinola J., Fossale E., Gillis T., Lopez E., Myers R.H., MacDonald M.E., Wheeler V.C. Genetic background modifies nuclear mutant huntingtin accumulation and HD CAG repeat instability in Huntington's disease knock-in mice. Hum. Mol. Genet. 2006, 15(12):2015-2024.
165. Lodi R., Schapira A.H., Manners D., Styles P., Wood N.W., Taylor D.J., Warner T.T. Abnormal in vivo skeletal muscle energy metabolism in Huntington's disease and dentatorubropallidoluysian atrophy. Ann. Neurol. 2000, 48:72-76.
166. 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.
167. Lunkes A., Mandel J.L. A cellular model that recapitulates major pathogenic steps of Huntington's disease. Hum. Mol. Genet. 1998, 7:1355-1361.
168. Luo S., Vacher C., Davies J.E., Rubinsztein D.C. Cdk5 phosphorylation of huntingtin reduces its cleavage by caspases: implications for mutant huntingtin toxicity. J. Cell Biol. 2005, 169:647-656.
169. 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 b, 11:1911-1926.
170. 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.
171. Luthi-Carter R., Strand A.D., Hanson S.A., Kooperberg C., Schilling G., La Spada A.R., Merry D.E., Young A.B., Ross C.A., Borchelt D.R., Olson J.M. Polyglutamine and transcription: gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects. Hum. Mol. Genet. 2002 a, 11:1927-1937.
172. Maat-Schieman M.L., Dorsman J.C., Smoor M.A., Siesling S., Van Duinen S.G., Verschuuren J.J., den Dunnen J.T., Van Ommen G.J., Roos R.A. Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. J. Neuropathol. Exp. Neurol. 1999, 58:129-137.
173. MacGibbon G.A., Hamilton L.C., Crocker S.F., Costain W.J., Murphy K.M., Robertson H.A., Denovan-Wright E.M. Immediate-early gene response to methamphetamine, haloperidol, and quinolinic acid is not impaired in Huntington's disease transgenic mice. J. Neurosci. Res. 2002, 67:372-378.
174. Mahant N., McCusker E.A., Byth K., Graham S. Huntington's disease: clinical correlates of disability and progression. Neurology 2003, 61:1085-1092.
175. 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.
176. Manley K., Shirley T.L., Flaherty L., Messer A. Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice. Nat. Genet. 1999, 23:471-473.
177. Martin W.R., Clark C., Ammann W., Stoessl A.J., Shtybel W., Hayden M.R. Cortical glucose metabolism in Huntington's disease. Neurology 1992, 42:223-229.
178. Martin-Aparicio E., Yamamoto A., Hernandez F., Hen R., Avila J., Lucas J.J. Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J. Neurosci. J1 - Jnsci J2 - JN 2001, 21:8772-8781.
179. 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. Gen. 1998, 18:150-154.
180. Martinez-Vicente M., Talloczy Z., Wong E., Tang G., Koga H., Kaushik S., de Vries R., Arias E., Harris S., Sulzer D., Cuervo A.M. Cargo recognition failure is responsible for inefficient autophagy in Huntington's disease. Nat. Neurosci. 2010, 13:567-576.
181. Mastroberardino P.G., Iannicola C., Nardacci R., Bernassola F., De Laurenzi V., Melino G., Moreno S., Pavone F., Oliverio S., Fesus L., Piacentini M. 'Tissue' transglutaminase ablation reduces neuronal death and prolongs survival in a mouse model of Huntington's disease. Cell Death Differ. 2002, 9:873-880.
182. Maynard C.J., Bottcher C., Ortega Z., Smith R., Florea B.I., Diaz-Hernandez M., Brundin P., Overkleeft H.S., Li J.Y., Lucas J.J., Dantuma N.P. Accumulation of ubiquitin conjugates in a polyglutamine disease model occurs without global ubiquitin/proteasome system impairment. Proc. Natl. Acad. Sci. USA 2009, 106:13986-13991.
183. McGeer E.G., McGeer P.L. Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids. Nature 1976, 263:517-519.
184. McMurray C.T. Mechanisms of trinucleotide repeat instability during human development. Nat. Rev. Genet. 2010, 11:786-799.
185. Menalled L.B., Sison J.D., Wu Y., Olivieri M., Li X.J., Li H., Zeitlin S., Chesselet M.F. Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J. Neurosci.: Official J. Soc.Neurosci. 2002, 22:8266-8276.
186. Menalled L.B., Sison J.D., Dragatsis I., Zeitlin S., Chesselet M.F. Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats. J. Comparative Neurol. 2003, 465:11-26.
187. Mestre T., Ferreira J., Coelho M.M., Rosa M., Sampaio C. Therapeutic interventions for symptomatic treatment in Huntington's disease. Cochrane Database Syst. Rev. 2009, CD006456.
188. Metzler M., Gan L., Wong T.P., Liu L., Helm J., Georgiou J., Wang Y., Bissada N., Cheng K., Roder J.C., Wang Y.T., Hayden M.R. NMDA receptor function and NMDA receptor-dependent phosphorylation of huntingtin is altered by the endocytic protein HIP1. J. Neurosci.: Official J. Soc.Neurosci. 2007, 27:2298-2308.
189. Metzler M., Gan L., Mazarei G., Graham R.K., Liu L., Bissada N., Lu G., Leavitt B.R., Hayden M.R. Phosphorylation of huntingtin at Ser421 in YAC128 neurons is associated with protection of YAC128 neurons from NMDA-mediated excitotoxicity and is modulated by PP1 and PP2A. J. Neurosci.: Official J. Soc. Neurosci. 2010, 30:14318-14329.
190. Milakovic T., Johnson G.V. Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin. J. Biol. Chem. 2005, 280:30773-30782.
191. Miller J.P., Holcomb J., Al-Ramahi I., de Haro M., Gafni J., Zhang N., Kim E., Sanhueza M., Torcassi C., Kwak S., Botas J., Hughes R.E., Ellerby L.M. Matrix metalloproteinases are modifiers of huntingtin proteolysis and toxicity in Huntington's disease. Neuron 2010, 67:199-212.
192. Milnerwood A.J., Gladding C.M., Pouladi M.A., Kaufman A.M., Hines R.M., Boyd J.D., Ko R.W., Vasuta O.C., Graham R.K., Hayden M.R., Murphy T.H., Raymond L.A. Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice. Neuron 2010, 65:178-190.
193. Mitra S., Tsvetkov A.S., Finkbeiner S. Single neuron ubiquitin-proteasome dynamics accompanying inclusion body formation in huntington disease. J. Biol. Chem. 2009, 284:4398-4403.
194. Modregger J., DiProspero N.A., Charles V., Tagle D.A., Plomann M. PACSIN 1 interacts with huntingtin and is absent from synaptic varicosities in presymptomatic Huntington's disease brains. Hum. Mol. Gen. 2002, 11:2547-2558.
195. Moffitt H., McPhail G.D., Woodman B., Hobbs C., Bates G.P. Formation of polyglutamine inclusions in a wide range of non-CNS tissues in the HdhQ150 knock-in mouse model of Huntington's disease. PLoS One 2009, 4:e8025.
196. Morfini G.A., You Y.M., Pollema S.L., Kaminska A., Liu K., Yoshioka K., Bjorkblom B., Coffey E.T., Bagnato C., Han D., Huang C.F., Banker G., Pigino G., Brady S.T. Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nat. Neurosci. 2009, 12:864-871.
197. 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 Huntington's disease. Eur. J. Neurosci. 2005, 21:855-870.
198. Morton A.J., Lagan M.A., Skepper J.N., Dunnett S.B. Progressive formation of inclusions in the striatum and hippocampus of mice transgenic for the human Huntington's disease mutation. J. Neurocytol. 2000, 29:679-702.
199. Morton A.J., Leavens W. Mice transgenic for the human Huntington's disease mutation have reduced sensitivity to kainic acid toxicity. Brain Res. Bull 2000, 52:51-59.
200. Neuwald A.F., Hirano T. HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions. Gen. Res. 2000, 10:1445-1452.
201. Norris P.J., Waldvogel H.J., Faull R.L., Love D.R., Emson P.C. Decreased neuronal nitric oxide synthase messenger RNA and somatostatin messenger RNA in the striatum of Huntington's disease. Neuroscience 1996, 72:1037-1047.
202. Nucifora F.C., Sasaki M., Peters M.F., Huang H., Cooper J.K., Yamada M., Takahashi H., Tsuji S., Troncoso J., Dawson V.L. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science (New York, NY) 2001, 291:2423-2428.
203. Okamoto S., Pouladi M.A., Talantova M., Yao D., Xia P., Ehrnhoefer D.E., Zaidi R., Clemente A., Kaul M., Graham R.K., Zhang D., Vincent Chen H.S., Tong G., Hayden M.R., Lipton S.A. Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat. Med. 2009, 15:1407-1413.
204. Oliveira J.M. Nature and cause of mitochondrial dysfunction in Huntington's disease: focusing on huntingtin and the striatum. J. Neurochem. 2010, 114:1-12.
205. Oliveira J.M., Jekabsons M.B., Chen S., Lin A., Rego A.C., Goncalves J., Ellerby L.M., Nicholls D.G. Mitochondrial dysfunction in Huntington's disease: the bioenergetics of isolated and in situ mitochondria from transgenic mice. J. Neurochem. 2007, 101:241-249.
206. Olshina M.A., Angley L.M., Ramdzan Y.M., Tang J., Bailey M.F., Hill A.F., Hatters D.M. Tracking mutant huntingtin aggregation kinetics in cells reveals three major populations that include an invariant oligomer pool. J. Biol. Chem. 2010, 285:21807-21816.
207. Orr H.T., Zoghbi H.Y. Trinucleotide Repeat Disorders. Ann. Rev. Neurosci. 2007, 30:575-621.
208. Ortega Z., Díaz-Hernández M., Lucas J.J. Is the ubiquitin-proteasome system impaired in Huntington's disease?. Cell Mol Life Sci. 2007, 64(17):2245-2257.
209. Pal A., Severin F., Lommer B., Shevchenko A., Zerial M. Huntingtin-HAP40 complex is a novel Rab5 effector that regulates early endosome motility and is up-regulated in Huntington's disease. J. Cell Biol. 2006, 172:605-618.
210. Pallos J., Bodai L., Lukacsovich T., Purcell J.M., Steffan J.S., Thompson L.M., Marsh J.L. Inhibition of specific HDACs and sirtuins suppresses pathogenesis in a Drosophila model of Huntington's disease. Hum. Mol. Genet. 2008, 17:3767-3775.
211. Panov A.V., Gutekunst C.-A., Leavitt B.R., Hayden M.R., Burke J.R., Strittmatter W.J., Greenamyre J.T. Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines. Nat. Neurosci. 2002, 5:731-736.
212. Pardo R., Colin E., Regulier E., Aebischer P., Deglon N., Humbert S., Saudou F. Inhibition of calcineurin by FK506 protects against polyglutamine-huntingtin toxicity through an increase of huntingtin phosphorylation at S421. J. Neurosci.: Official J. Soc.Neurosci. 2006, 26:1635-1645.
213. Pardo R., Molina-Calavita M., Poizat G., Keryer G., Humbert S., Saudou F. pARIS-htt: an optimised expression platform to study huntingtin reveals functional domains required for vesicular trafficking. Mol. Brain 2010, 3:17.
214. 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.
215. Parker W.D., Boyson S.J., Luder A.S., Parks J.K. Evidence for a defect in NADH: ubiquinone oxidoreductase (complex I) in Huntington's disease. Neurology 1990, 40:1231-1234.
216. Persichetti F., Carlee L., Faber P.W., McNeil S.M., Ambrose C.M., Srinidhi J., Anderson M., Barnes G.T., Gusella J.F., MacDonald M.E. Differential expression of normal and mutant Huntington's disease gene alleles. Neurobiol. Dis. 1996, 3:183-190.
217. Perutz M.F. Glutamine repeats and inherited neurodegenerative diseases: molecular aspects. Curr. Opin. Struct. Biol. 1996, 6:848-858.
218. 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.
219. Peters M.F., Nucifora F.C., Kushi J., Seaman H.C., Cooper J.K., Herring W.J., Dawson V.L., Dawson T.M., Ross C.A. Nuclear targeting of mutant Huntingtin increases toxicity. Mol. Cell. Neurosci. 1999, 14:121-128.
220. Peters M.F., Ross C.A. Isolation of a 40-kDa Huntingtin-associated protein. J. Biol. Chem. 2001, 276:3188-3194.
221. Pfister E.L., Kennington L., Straubhaar J., Wagh S., Liu W., DiFiglia M., Landwehrmeyer B., Vonsattel J.-P., Zamore P.D., Aronin N. Five siRNAs targeting three SNPs may provide therapy for three-quarters of Huntington's idsease patients. Curr. Biol. 2009, 19:774-778.
222. Pfister E.L., Zamore P.D. Huntington's disease: silencing a brutal killer. Exp. Neurol. 2009, 220:226-229.
223. Qin Z.H., Wang Y., Kegel K.B., Kazantsev A., Apostol B.L., Thompson L.M., Yoder J., Aronin N., DiFiglia M. Autophagy regulates the processing of amino terminal huntingtin fragments. Hum. Mol. Gen. 2003, 12:3231-3244.
224. Qin Z.H., Wang Y., Sapp E., Cuiffo B., Wanker E., Hayden M.R., Kegel K.B., Aronin N., DiFiglia M. Huntingtin bodies sequester vesicle-associated proteins by a polyproline-dependent interaction. J. Neurosci. 2004, 24(1):269-281.
225. Ramdzan Y.M., Nisbet R.M., Miller J., Finkbeiner S., Hill A.F., Hatters D.M. Conformation sensors that distinguish monomeric proteins from oligomers in live cells. Chem. Biol. 2010, 17:371-379.
226. Rangone H., Poizat G., Troncoso J., Ross C.A., MacDonald M.E., Saudou F., Humbert S. The serum- and glucocorticoid-induced kinase SGK inhibits mutant huntingtin-induced toxicity by phosphorylating serine 421 of huntingtin. Eur. J. Neurosci. 2004, 19:273-279.
227. Ratovitski T., Nakamura M., D'Ambola J., Chighladze E., Liang Y., Wang W., Graham R., Hayden M.R., Borchelt D.R., Hirschhorn R.R., Ross C.A. N-terminal proteolysis of full-length mutant huntingtin in an inducible PC12 cell model of Huntington's disease. Cell Cycle 2007, 6:2970-2981.
228. Ravache M., Weber C., Merienne K., Trottier Y. Transcriptional activation of REST by Sp1 in Huntington's disease models. PLoS One 2010, 5:e14311.
229. Ravikumar B., Duden R., Rubinsztein D.C. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum. Mol. Gen. 2002, 11:1107-1117.
230. Ravikumar B., Moreau K., Jahreiss L., Puri C., Rubinsztein D.C. Plasma membrane contributes to the formation of pre-autophagosomal structures. Nat. Cell Biol. 2010, 12:747-757.
231. Ravikumar B., Sarkar S., Rubinsztein D.C. Clearance of mutant aggregate-prone proteins by autophagy. Methods Mol. Biol. 2008, 445:195-211.
232. 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. Gen. 2004, 36:585-595.
233. 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.
234. Reynolds N.C., Prost R.W., Mark L.P. Heterogeneity in 1H-MRS profiles of presymptomatic and early manifest Huntington's disease. Brain Res. 2005, 1031:82-89.
235. Richfield E.K., Maguire-Zeiss K.A., Cox C., Gilmore J., Voorn P. Reduced expression of preproenkephalin in striatal neurons from Huntington's disease patients. Ann. Neurol. 1995, 37:335-343.
236. Roizin L., Stellar S., Liu J.C. Advances in neurology 1979, Vol. 23:95-122. Raven Press, New York.
237. Runne H., Kuhn A., Wild E.J., Pratyaksha W., Kristiansen M., Isaacs J.D., Regulier E., Delorenzi M., Tabrizi S.J., Luthi-Carter R. Analysis of potential transcriptomic biomarkers for Huntington's disease in peripheral blood. Proc. Natl. Acad. Sci. USA 2007, 104:14424-14429.
238. Runne H., Regulier E., Kuhn A., Zala D., Gokce O., Perrin V., Sick B., Aebischer P., Deglon N., Luthi-Carter R. Dysregulation of gene expression in primary neuron models of huntington's disease shows that polyglutamine-related effects on the striatal transcriptome may not be dependent on brain circuitry. J. Neurosci. 2008, 28:9723-9731.
239. Sadri-Vakili G., Menon A.S., Farrell L.A., Keller-McGandy C.E., Cantuti-Castelvetri I., Standaert D.G., Augood S.J., Yohrling G.J., Cha J.H. Huntingtin inclusions do not down-regulate specific genes in the R6/2 Huntington's disease mouse. Eur. J. Neurosci. 2006, 23:3171-3175.
240. Salinas S., Bilsland L.G., Schiavo G. Molecular landmarks along the axonal route: axonal transport in health and disease. Curr. Opin. Cell. Biol. 2008, 20:445-453.
241. Sanchez Mejia R.O., Friedlander R.M. Caspases in Huntington's disease. Neuroscientist: Rev. J. Bringing Neurobiol., Neurol. Psychiatry 2001, 7:480-489.
242. Sanchez-Pernaute R., Garcia-Segura J.M., del Barrio Alba A., Viano J., de Yebenes J.G. Clinical correlation of striatal 1H MRS changes in Huntington's disease. Neurology 1999, 53:806-812.
243. Sapp E., Schwarz C., Chase K., Bhide P.G., Young A.B., Penney J., Vonsattel J.P., Aronin N., DiFiglia M. Huntingtin localization in brains of normal and Huntington's disease patients. Ann. Neurol. 1997, 42:604-612.
244. Sarkar S., Rubinsztein D.C. Huntington's disease: degradation of mutant huntingtin by autophagy. FEBS J. 2008, 275:4263-4270.
245. Sathasivam, K., Hobbs, C., Turmaine, M., Mangiarini, L., Mahal, A., Bertaux, F., Wanker, E.E., Doherty, P., Davies, S.W. and Bates, G.P. (1999). Formation of polyglutamine inclusions in non-CNS tissue [In Process Citation]. t8: 813-822.
246. Sathasivam K., Lane A., Legleiter J., Warley A., Woodman B., Finkbeiner S., Paganetti P., Muchowski P.J., Wilson S., Bates G.P. Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease. Hum. Mol. Gen. 2010, 19:65-78.
247. 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.
248. Savas J.N., Ma B., Deinhardt K., Culver B.P., Restituito S., Wu L., Belasco J.G., Chao M.V., Tanese N. A role for huntington disease protein in dendritic RNA granules. J. Biol. Chem. 2010, 285:13142-13153.
249. Sawa A., Nagata E., Sutcliffe S., Dulloor P., Cascio M.B., Ozeki Y., Roy S., Ross C.A., Snyder S.H. Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington's disease patient lymphoblasts. Neurobiol. Dis. 2005, 20:267-274.
250. Sawa A., Wiegand G.W., Cooper J., Margolis R.L., Sharp A.H., Lawler J.F., Greenamyre J.T., Snyder S.H., Ross C.A. Increased apoptosis of Huntington disease lymphoblasts associated with repeat length-dependent mitochondrial depolarization. Nat. Med. 1999, 5:1194-1198.
251. 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.
252. 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.
253. 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. Movement Disorders: Official J. Movement Disorder Soc. 2002, 17:748-757.
254. Schilling B., Gafni J., Torcassi C., Cong X., Row R.H., LaFevre-Bernt M.A., Cusack M.P., Ratovitski T., Hirschhorn R., Ross C.A., Gibson B.W., Ellerby L.M. Huntingtin phosphorylation sites mapped by mass spectrometry. Modulation of cleavage and toxicity. J. Biol. Chem. 2006, 281:23686-23697.
255. 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.
256. Schwarcz R., Foster A.C., French E.D., Whetsell W.O., Kohler C. Excitotoxic models for neurodegenerative disorders. Life Sci. 1984, 35:19-32.
257. Schwarcz R., Guidetti P., Sathyasaikumar K.V., Muchowski P.J. Of mice, rats and men: Revisiting the quinolinic acid hypothesis of Huntington's disease. Prog Neurobiol 2010, 90(2):230-245.
258. Schwartz A.L., Ciechanover A. Targeting proteins for destruction by the ubiquitin system: implications for human pathobiology. Ann. Rev. Pharmacol. Toxicol. 2009, 49:73-96.
259. Semaka A., Collins J.A., Hayden M.R. Unstable familial transmissions of Huntington disease alleles with 27-35 CAG repeats (intermediate alleles). Am. J. Med. Genet. Part B: Neuropsychiatric Gen. 2010, 153B:314-320.
260. Seo H., Kim W., Isacson O. Compensatory changes in the ubiquitin-proteasome system, brain-derived neurotrophic factor and mitochondrial complex II/III in YAC72 and R6/2 transgenic mice partially model Huntington's disease patients. Hum. Mol. Gen. 2008, 17:3144-3153.
261. Seo H., Sonntag K.C., Isacson O. Generalized brain and skin proteasome inhibition in Huntington's disease. Annals Neurol. 2004, 56:319-328.
262. Seo H., Sonntag K.C., Kim W., Cattaneo E., Isacson O. Proteasome activator enhances survival of Huntington's disease neuronal model cells. PLoS One 2007, 2:e238.
263. Seong I.S., Ivanova E., Lee J.M., Choo Y.S., Fossale E., Anderson M., Gusella J.F., Laramie J.M., Myers R.H., Lesort M., MacDonald M.E. HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism. Hum. Mol. Genet. 2005, 14:2871-2880.
264. Shao J., Diamond M.I. Polyglutamine diseases: emerging concepts in pathogenesis and therapy. Hum. Mol. Genet. 2007, 16:R115-R123.
265. Shehadeh J., Fernandes H.B., Zeron Mullins M.M., Graham R.K., Leavitt B.R., Hayden M.R., Raymond L.A. Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease. Neurobiol Dis 2006, 21:392-403.
266. Shelbourne, P. F., Keller-McGandy, C., Bi, W.L., Yoon, S. R., Dubeau, L., Veitch, N. J., Vonsattel, J. P., Wexler, N.S., US-Venezuela Collaborative Research Group, Arnheim, N. and Augood, S. J. (2007). Triplet repeat mutation length gains correlate with cell-type specific vulnerability in Huntington disease brain. Hum. Mol. Genet. 16(10): 1133-1142.
267. Shelbourne 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(5):763-774.
268. 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., Aoyagi Y., Hozumi I., Nagatsu T., Takiyama Y., Nishizawa M., Goto J., Kanazawa 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.
269. Sieradzan K.A., Mechan A.O., Jones L., Wanker E.E., Nukina N., Mann D.M. Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp. Neurol. 1999, 156:92-99.
270. Silvestroni A., Faull R.L., Strand A.D., Moller T. Distinct neuroinflammatory profile in post-mortem human Huntington's disease. Neuroreport 2009, 20:1098-1103.
271. Sinadinos C., Burbidge-King T., Soh D., Thompson L.M., Marsh J.L., Wyttenbach A., Mudher A.K. Live axonal transport disruption by mutant huntingtin fragments in Drosophila motor neuron axons. Neurobiol. Dis. 2009, 34:389-395.
272. Singaraja R.R., Hadano S., Metzler M., Givan S., Wellington C.L., Warby S., Yanai A., Gutekunst C.A., Leavitt B.R., Yi H., Fichter K., Gan L., McCutcheon K., Chopra V., Michel J., Hersch S.M., Ikeda J.E., Hayden M.R. HIP14, a novel ankyrin domain-containing protein, links huntingtin to intracellular trafficking and endocytosis. Hum. Mol. Genet. 2002, 11:2815-2828.
273. Sipione S., Rigamonti D., Valenza M., Zuccato C., Conti L., Pritchard J., Kooperberg C., Olson J.M., Cattaneo E. Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses. Hum. Mol. Genet. 2002, 11:1953-1965.
274. 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.
275. Smith R., Bacos K., Fedele V., Soulet D., Walz H.A., Obermuller S., Lindqvist A., Bjorkqvist M., Klein P., Onnerfjord P., Brundin P., Mulder H., Li J.Y. Mutant huntingtin interacts with {beta}-tubulin and disrupts vesicular transport and insulin secretion. Hum. Mol. Gen. 2009, 18:3942-3954.
276. Steffan J.S., Agrawal N., Pallos J., Rockabrand E., Trotman L.C., Slepko N., Illes K., Lukacsovich T., Zhu Y.Z., Cattaneo E., Pandolfi P.P., Thompson L.M., Marsh J.L. SUMO modification of Huntingtin and Huntington's disease pathology. Science 2004, 304:100-104.
277. 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 neurodegeneration in Drosophila. Nature 2001, 413:739-743.
278. 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.
279. Strand A.D., Aragaki A.K., Shaw D., Bird T., Holton J., Turner C., Tapscott S.J., Tabrizi S.J., Schapira A.H., Kooperberg C., Olson J.M. Gene expression in Huntington's disease skeletal muscle: a potential biomarker. Hum. Mol. Genet. 2005, 14:1863-1876.
280. Swami M., Hendricks A.E., Gillis T., Massood T., Mysore J., Myers R.H., Wheeler V.C. Somatic expansion of the Huntington's disease CAG repeat in the brain is associated with an earlier age of disease onset. Hum. Mol. Genet. 2009, 18:3039-3047.
281. Szebenyi G., Morfini G.A., Babcock A., Gould M., Selkoe K., Stenoien D.L., Young M., Faber P.W., MacDonald M.E., McPhaul M.J., Brady S.T. Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 2003, 40:41-52.
282. Tabrizi S.J., Scahill R.I., Durr A., Roos R.A.C., Leavitt B.R., Jones R., Landwehrmeyer G.B., Fox N.C., Johnson H., Hicks S.L., Kennard C., Craufurd D., Frost C., Langbehn D.R., Reilmann R., Stout J.C. 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.
283. Tabrizi S.J., Workman J., Hart P.E., Mangiarini L., Mahal A., Bates G., Cooper J.M., Schapira A.H. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann. Neurol. 2000, 47:80-86.
284. Takano H., Gusella J.F. The predominantly HEAT-like motif structure of huntingtin and its association and coincident nuclear entry with dorsal, an NF-kB/Rel/dorsal family transcription factor. BMC Neurosci. 2002, 3:15.
285. Tanaka Y., Igarashi S., Nakamura M., Gafni J., Torcassi C., Schilling G., Crippen D., Wood J.D., Sawa A., Jenkins N.A., Copeland N.G., Borchelt D.R., Ross C.A., Ellerby L.M. Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin. Neurobiol. Dis. 2006, 21:381-391.
286. Tasdemir E., Maiuri M.C., Orhon I., Kepp O., Morselli E., Criollo A., Kroemer G. p53 represses autophagy in a cell cycle-dependent fashion. Cell Cycle 2008, 7:3006-3011.
287. Telenius H., Kremer B., Goldberg Y.P., Theilmann J., Andrew S.E., Zeisler J., Adam S., Greenberg C., Ives E.J., Clarke L.A., Hayden M.R. Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat. Genet. 1994, 6:409-414.
288. Thakur A.K., Jayaraman M., Mishra R., Thakur M., Chellgren V.M., Byeon I.J., Anjum D.H., Kodali R., Creamer T.P., Conway J.F., Gronenborn A.M., Wetzel R. Polyglutamine disruption of the huntingtin exon 1 N terminus triggers a complex aggregation mechanism. Nat. Struct. Mol. Biol. 2009, 16:380-389.
289. Thomas E.A., Coppola G., Desplats P.A., Tang B., Soragni E., Burnett R., Gao F., Fitzgerald K.M., Borok J.F., Herman D., Geschwind D.H., Gottesfeld J.M. 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.
290. Thomas E.A., Coppola G., Tang B., Kuhn A., Kim S., Geschwind D.H., Brown T.B., Luthi-Carter R., Ehrlich M.E. In vivo cell-autonomous transcriptional abnormalities revealed in mice expressing mutant huntingtin in striatal but not cortical neurons. Hum. Mol. Genet. 2011.
291. Thompson L.M., Aiken C.T., Kaltenbach L.S., Agrawal N., Illes K., Khoshnan A., Martinez-Vincente M., Arrasate M., O'Rourke J.G., Khashwji H., Lukacsovich T., Zhu Y.Z., Lau A.L., Massey A., Hayden M.R., Zeitlin S.O., Finkbeiner S., Green K.N., LaFerla F.M., Bates G., Huang L., Patterson P.H., Lo D.C., Cuervo A.M., Marsh J.L., Steffan J.S. IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. J. Cell Biol. 2009, 187:1083-1099.
292. Todd P.K., Paulson H.L. RNA-mediated neurodegeneration in repeat expansion disorders. Ann. Neurol. 2010, 67:291-300.
293. Truant R., Atwal R.S., Burtnik A. Nucleocytoplasmic trafficking and transcription effects of huntingtin in Huntington's disease. Prog. Neurobiol. 2007, 83:211-227.
294. Trushina E., Dyer R.B., Badger J.D., 2nd, Ure D., Eide L., Tran D.D., Vrieze B.T., Legendre-Guillemin V., McPherson P.S., Mandavilli B.S., Van Houten B., Zeitlin S., McNiven M., Aebersold R., Hayden M., Parisi J.E., Seeberg E., Dragatsis I., Doyle K., Bender A., Chacko C., McMurray C.T. Mutant huntingtin impairs axonal trafficking in mammalian neurons in vivo and in vitro. Mol. Cell. Biol. 2004, 24:8195-8209.
295. Trushina E., Heldebrant M.P., Perez-Terzic C.M., Bortolon R., Kovtun I.V., Badger J.D., Terzic A., Estevez A., Windebank A.J., Dyer R.B., Yao J., McMurray C.T. Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease. Proc. Natl. Acad. Sci. USA 2003, 100:12171-12176.
296. Turmaine M., Raza A., Mahal A., Mangiarini L., Bates G.P., Davies S.W. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc. Natl. Acad. Sci. USA 2000, 97:8093-8097.
297. Turner C., Cooper J.M., Schapira A.H. Clinical correlates of mitochondrial function in Huntington's disease muscle. Movement Disorders: Official J. Movement Disorder Soc. 2007, 22:1715-1721.
298. Twelvetrees A.E., Yuen E.Y., Arancibia-Carcamo I.L., MacAskill A.F., Rostaing P., Lumb M.J., Humbert S., Triller A., Saudou F., Yan Z., Kittler J.T. Delivery of GABAARs to synapses is mediated by HAP1-KIF5 and disrupted by mutant huntingtin. Neuron 2010, 65:53-65.
299. Vatsavayai S.C., Dallérac G.M., Milnerwood A.J., Cummings D.M., Rezaie P., Murphy K.P., Hirst M.C. Progressive CAG expansion in the brain of a novel R6/1-89Q mouse model of Huntington's disease with delayed phenotypic onset. Brain Res Bull 2006, 72(2-3):98-102.
300. Veitch N.J., Ennis M., McAbney J.P., Shelbourne P.F., Monckton D.G. Inherited CAG·CTG allele length is a major modifier of somatic mutation length variability in Huntington disease. DNA Repair 2007, 6:789-796.
301. 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.
302. Ventruti A., Cuervo A.M. Autophagy and neurodegeneration. Curr. Neurol. Neurosci. Rep. 2007, 7:443-451.
303. Vonsattel J.P., DiFiglia M. Huntington disease. J. Neuropathol.Exp. Neurol. 1998, 57:369-384.
304. Vonsattel J.P., Myers R.H., Stevens T.J., Ferrante R.J., Bird E.D., Richardson E.P. Neuropathological classification of Huntington's disease. J. Neuropathol. Exp. Neurol. 1985, 44:559-577.
305. Waelter S., Boeddrich A., Lurz R., Scherzinger E., Lueder G., Lehrach H., Wanker E.E. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol. Biol. Cell 2001 a, 12:1393-1407.
306. Waelter S., Scherzinger E., Hasenbank R., Nordhoff E., Lurz R., Goehler H., Gauss C., Sathasivam K., Bates G.P., Lehrach H., Wanker E.E. The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Hum. Mol. Genet. 2001 b, 10:1807-1817.
307. Wang J., Martin E., Gonzales V., Borchelt D.R., Lee M.K. Differential regulation of small heat shock proteins in transgenic mouse models of neurodegenerative diseases. Neurobiol. Aging 2008, 29:586-597.
308. Wanker E.E., Rovira C., Scherzinger E., Hasenbank R., Walter S., Tait D., Colicelli J., Lehrach H. HIP-I: a huntingtin interacting protein isolated by the yeast two- hybrid system. Hum. Mol. Genet. 1997, 6:487-495.
309. Warby S.C., Chan E.Y., Metzler M., Gan L., Singaraja R.R., Crocker S.F., Robertson H.A., Hayden M.R. Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo. Hum. Mol. Genet. 2005, 14:1569-1577.
310. Warby S.C., Doty C.N., Graham R.K., Carroll J.B., Yang Y.-Z., Singaraja R.R., Overall C.M., Hayden M.R. Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus. Hum. Mol. Gen. 2008, 17:2390-2404.
311. Wareski P., Vaarmann A., Choubey V., Safiulina D., Liiv J., Kuum M., Kaasik A. PGC-1α and PGC-1β regulate mitochondrial density in neurons. J. Biol. Chem. 2009, 284:21379-21385.
312. Warrick J.M., Paulson H.L., Gray-Board G.L., Bui Q.T., Fischbeck K.H., Pittman R.N., Bonini N.M. Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell 1998, 93:939-949.
313. Wellington C.L., Ellerby L.M., Gutekunst C.A., Rogers D., Warby S., Graham R.K., Loubser O., van Raamsdonk J., Singaraja R., Yang Y.Z., Gafni J., Bredesen D., Hersch S.M., Leavitt B.R., Roy S., Nicholson D.W., Hayden M.R. Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J. Neurosci.: Official J. Soc.Neurosci. 2002, 22:7862-7872.
314. Wellington C.L., Hayden M.R. Caspases and neurodegeneration: on the cutting edge of new therapeutic approaches. Clin. Genet. 2000, 57:1-10.
315. Weydt P., Pineda V.V., Torrence A.E., Libby R.T., Satterfield T.F., Lazarowski E.R., Gilbert M.L., Morton G.J., Bammler T.K., Strand A.D. Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1alpha in Huntington's disease neurodegeneration. Cell Metabolism 2006, 4:349-362.
316. Weydt P., Soyal S.M., Gellera C., Didonato S., Weidinger C., Oberkofler H., Landwehrmeyer G.B., Patsch W. The gene coding for PGC-1alpha modifies age at onset in Huntington's disease. Mol. Neurodeg. 2009, 4:3.
317. Wheeler V.C., Lebel L.A., Vrbanac V., Teed A., te Riele H., MacDonald M.E. Mismatch repair gene Msh2 modifies the timing of early disease in Hdh(Q111) striatum. Hum. Mol. Genet. 2003, 12:273-281.
318. 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.
319. Woodman B., Butler R., Landles C., Lupton M.K., Tse J., Hockly E., Moffitt H., Sathasivam K., Bates G.P. The Hdh(Q150/Q150) knock-in mouse model of HD and the R6/2 exon 1 model develop comparable and widespread molecular phenotypes. Brain Res. Bull. J1 - BRB 2007, 72:83-97.
320. Wyttenbach A., Carmichael J., Swartz J., Furlong R.A., Narain Y., Rankin J., Rubinsztein D.C. Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease. Proc. Natl. Acad. Sci. USA 2000, 97:2898-2903.
321. Xia J., Lee D.H., Taylor J., Vandelft M., Truant R. Huntingtin contains a highly conserved nuclear export signal. Hum. Mol. Genet. 2003, 12:1393-1403.
322. 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.
323. Yanai A., Huang K., Kang R., Singaraja R.R., Arstikaitis P., Gan L., Orban P.C., Mullard A., Cowan C.M., Raymond L.A., Drisdel R.C., Green W.N., Ravikumar B., Rubinsztein D.C., El-Husseini A., Hayden M.R. Palmitoylation of huntingtin by HIP14 is essential for its trafficking and function. Nat. Neurosci. 2006, 9:824-831.
324. Yang W., Dunlap J.R., Andrews R.B., Wetzel R. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum. Mol. Gen. 2002, 11:2905-2917.
325. Yang Y.P., Liang Z.Q., Gu Z.L., Qin Z.H. Molecular mechanism and regulation of autophagy. Acta Pharmacol. Sin 2005, 26:1421-1434.
326. Yao T.P. The role of ubiquitin in autophagy-dependent protein aggregate processing. Genes Cancer 2010, 1:779-786.
327. Young A.B., Greenamyre J.T., Hollingsworth Z., Albin R., D'Amato C., Shoulson I., Penney J.B. NMDA receptor losses in putamen from patients with Huntington's disease. Science 1988, 241:981-983.
328. Zala D., Colin E., Rangone H., Liot G., Humbert S., Saudou F. Phosphorylation of mutant huntingtin at S421 restores anterograde and retrograde transport in neurons. Hum. Mol. Gen. 2008, 17:3837-3846.
329. Zeron M.M., Chen N., Moshaver A., Lee A.T., Wellington C.L., Hayden M.R., Raymond L.A. Mutant huntingtin enhances excitotoxic cell death. Mol. Cell. Neurosci. 2001, 17:41-53.
330. Zeron M.M., Fernandes H.B., Krebs C., Shehadeh J., Wellington C.L., Leavitt B.R., Baimbridge K.G., Hayden M.R., Raymond L.A. Potentiation of NMDA receptor-mediated excitotoxicity linked with intrinsic apoptotic pathway in YAC transgenic mouse model of Huntington's disease. Mol. Cell. Neurosci. 2004, 25:469-479.
331. Zeron M.M., Hansson O., Chen N., Wellington C.L., Leavitt B.R., Brundin P., Hayden M.R., Raymond L.A. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron 2002, 33:849-860.
332. Zhang Y., Ona V.O., Li M., Drozda M., Dubois-Dauphin M., Przedborski S., Ferrante R.J., Friedlander R.M. Sequential activation of individual caspases, and of alterations in Bcl-2 proapoptotic signals in a mouse model of Huntington's disease. J.. Neurochem. 2003, 87:1184-1192.
333. Zheng S., Clabough E.B., Sarkar S., Futter M., Rubinsztein D.C., Zeitlin S.O. Deletion of the huntingtin polyglutamine stretch enhances neuronal autophagy and longevity in mice. PLoS Gen. 2010, 6:e1000838.
334. 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.
335. Zucker B., Luthi-Carter R., Kama J.A., Dunah A.W., Stern E.A., Fox J.H., Standaert D.G., Young A.B., Augood S.J. Transcriptional dysregulation in striatal projection- and interneurons in a mouse model of Huntington's disease: neuronal selectivity and potential neuroprotective role of HAP1. Hum. Mol. Genet. 2005, 14:179-189.