Multiple pathways contribute to the pathogenesis of Huntington disease

Molecular Neurodegeneration

Volumn 1, Issue 1, 2006, Pages

  Li, Shihua ^a   Li, Xiao Jiang ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 34248166420     PISSN: None     EISSN: 17501326     Source Type: Journal    
DOI: 10.1186/1750-1326-1-19     Document Type: Review

References (147)

1. Martin JB, Gusella JF: Huntington's disease. Pathogenesis and management. N Engl J Med 1986, 315:1267-1276.
2. Harper PS: Huntington's disease 1991.
3. Folstein SE, Leigh RJ, Parhad IM, Folstein MF: The diagnosis of Huntington's disease. Neurology 1986, 36:1279-1283.
4. Shiwach RS, Norbury CG: A controlled psychiatric study of individuals at risk for Huntington's disease, Br J Psychiatry 1994, 165:500-505.
5. Chandler JH, Reed TE, Dejong RN: Huntington's chorea in Michigan. III. Clinical observations. Neurology I960, 10:148-153.
6. Foroud T, Gray J, Ivashina J, Conneally PM: Differences in duration of Huntington's disease based on age at onset. J Neural Neurosu r g Psychiatry 1999, 66:52-56.
7. HD collaborative research group: A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell 1993, 72:971-983.
8. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, Starr E, Squitieri F, Lin B, Kalchman MA, et al.: The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet 1993, 4:398-403.
9. Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M, et al.: Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet 1993, 4:387-392.
10. Snell RG, MacMillan JC, Cheadle JP, Fenton I, Lazarou LP, Davies P, MacDonald ME, Gusella JF, Harper PS, Shaw DJ: Relationship between trinucleotide repeat expansion and phenotypic variation in Huntington's disease. Nat Genet 1993, 4:393-397.
11. Zoghbi HY, Orr HT: Glutamine repeats and neurodegeneration. Annu Rev Neuroseci 2000, 23:217-247.
12. Gatchel JR, Zoghbi HY: Diseases of unstable repeat expansion: mechanisms and common principles. Nat Rev Genet 2005, 6:743-755.
13. Butler R, Bates GP: Histone deacetylase inhibitors as therapeutics for polyglutamine disorders. Nat Rev Neurosci 2006, 7:784-796.
14. Harjes P, Wanker EE: The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem Sci 2003, 28:425-433.
15. Clabough EB, Zeitlin SO: Deletion of the triplet repeat encoding polyglutamine within the mouse Huntington's disease gene results in subtle behavioral/motor phenotypes in vivo and elevated levels of ATP with cellular senescence in vitro. Hum Mol Genet 2006, 15:607-623.
16. Gutekunst CA, Levey AI, Heilman CJ, Whaley WL, Yi H, Nash NR, Rees HD, Madden JJ, Hersch SM: Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. Proc Natl Acod Sci USA 1995, 92:8710-8714.
17. DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, Martin E, Vonsattel JP, Carraway R, Reeves SA, et al.: Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 1995, 14:1075-1081.
18. Sharp AH, Loev SJ, Schilling G, Li SH, Li XJ, Bao J, Wagster MV, Kotzuk JA, Steiner JP, Lo A, et al.: Widespread expression of Huntington's disease gene (IT 15) protein product. Neuron 1995, 14:1065-1074.
19. Li SH. Li XJ: Huntingtin-protein interactions and the pathogenesis of Huntington's disease. Trends Genet 2004, 20:146-154.
20. Takano H, Gusella JF: 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.
21. Neuwald AF, Hirano T: HEAT repeats associated with condensins, cohesins, and other complexes involved in chromosome-related functions. Genome Res 2000, 10:1445-1452.
22. Gutekunst CA, Li SH, Yi H, Ferrante RJ, Li XJ, Hersch SM: The cellular and subcellular localization of huntingtin-associated protein I (HAPI): comparison with huntingtin in rat and human. J Neurosci 1998, 18:7674-7686.
23. Duyao MP, Auerbach AB, Ryan A, Persichetti F, Barnes GT, McNeil SM, Ge P, Vonsattel JP, Gusella JF, Joyner AL, et al.: Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 1995, 269:407-410.
24. Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR: Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 1995, 81:811-823.
25. Zeitlin S, Liu JP, Chapman DL, Papaioannou VE, Efstratiadis A: Increased apoptosis and early embryonic lethality in mice nullizygous for the Huntington's disease gene homologue. Nat Genet 1995, 11:155-163.
26. Dragatsis I, Levine MS, Zeitlin S: Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in mice. Nat Genet 2000, 26:300-306.
27. Cattaneo E, Rigamonti D, Goffredo D, Zuccato C, Squitieri F, Sipione S: Loss of normal huntingtin function: new developments in Huntington's disease research. Trends Neurosci 2001, 24:182-188.
28. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP: Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997, 90:537-548.
29. Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, Slum HH, Ratovitski T, Cooper JK, Jenkins NA, Copeland NG, Price DL, Ross CA, Borchelt DR: Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 1999, 8:397-407.
30. Hodgson JG, Smith DJ, McCutcheon K, Koide HE, Nishiyama K, Dinulos MB, Stevens ME, Bissada N, Nasir J, Kanazawa I, Disteche CM, Rubin EM, Hayden MR: Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype. Hum Mol Genet 1996, 5:1875-1885.
31. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr: Neuropathological classification of Huntington's disease. J Neuropathol Exp Neural 1985, 44:559-577.
32. Kremer HP, Roos RA, Dingjan G, Marani E, Bots GT: Atrophy of the hypothalamic lateral tuberal nucleus in Huntington's disease. J Neuropathol Exp Neural 1990, 49:371-382.
33. Ferrante RJ, Kowall NW, Beai MF, Richardson EP Jr, Bird ED, Martin JB: Selective sparing of a class of striatal neurons in Huntington's disease. Science 1985, 230:561-563.
34. Graveland GA, Williams RS, DiFiglia M: Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 1985, 227:770-773.
35. Myers RH, Vonsattel JP, Paskevich PA, Kiely DK, Stevens TJ, Cupples LA, Richardson EP Jr, Bird ED: Decreased neuronal and increased oligodendroglial densities in Huntington's disease caudate nucleus, J Neuropathol Exp Neural 1991, 50:729-742.
36. Singhrao SK, Thomas P, Wood JD, MacMillan JC, Neal JW, Harper PS, Jones AL: Huntingtin protein colocalizes with lesions of neurodegenerative diseases: An investigation in Huntington's, Alzheimer's, and Pick's diseases. Exp Neural 1998, 150:213-222.
37. Sapp E, Kegel KB, Aronin N, Hashikawa T, Uchiyama Y, Tohyama K, Bhide PG, Vonsattel JP, DiFiglia M: Early and progressive accumulation of reactive microglia in the Huntington disease brain. J Neuropathol Exp Neural 2001, 60:161-172.
38. Rajkowska G, Selemon LD, Goldman-Rakic PS: Neuronal and glial somal size in the prefrontal cortex: a postmortem morphometric study of schizophrenia and Huntington disease. Arch Gen Psychiatry 1998, 55:215-224.
39. 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, 65:289-297.
40. Yu ZX, Li SH, Evans J, Pillarisetti A, Li H, Li XJ: Mutant huntingtin causes context-dependent neurodegeneration in mice with Huntington's disease. J Neurosci 2003, 23:2193-2202.
41. Gu X, Li C, Wei W, Lo V, Gong S, Li SH, Iwasato T, Itohara S, Li XJ, Mody I, Heintz N, Yang XW: Pathological Cell-Cell Interactions Elicited by a Neuropathogenic Form of Mutant Huntingtin Contribute to Cortical Pathogenesis in HD Mice. Neuron 2005, 46:433-444.
42. Reddy PH, Williams M, Charles V, Garrett L, Pike-Buchanan L, Whetsell WO Jr, Miller G, Tagle DA: Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet 1998, 20:198-202.
43. Lin CH, Tallaksen-Greene S, Chien WM, Cearley JA, Jackson WS, Crouse AB, Ren S, Li XJ, Albin RL, Detloff PJ: Neurological abnormalities in a knock-in mouse model of Huntington's disease. Hum Mol Genet 2001, 10:137-144.
44. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N: Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997, 277:1990-1993.
45. Gutekunst CA. Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li XJ: Nuclear and neuropil aggregates in Huntington's disease: relationship to neuropathology. J Neurosci 1999, 19:2522-2534.
46. Kuemmerle S, Gutekunst CA, Klein AM, Li XJ, Li SH, Beal MF, Hersch SM, Ferrante RJ: Huntington aggregates may not predict neuronal death in Huntington's disease. Ann Neural 1999, 46:842-849.
47. Slow EJ, Graham RK, Osmand AP, Devon RS, Lu G, Deng Y, Pearson J. Vaid K, Bissada N, Wetzel R, Leavitt BR, Hayden MR: Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci U S A 2005, 102:11402-11407.
48. Saudou F, Finkbeiner S, Devys D, Greenberg ME: Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell 1998, 95:55-66.
49. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S: Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 2004, 431:805-810.
50. Li H, Li SH, Cheng AL, Mangiarini L, Bates GP, Li XJ: Ultrastructural localization and progressive formation of neuropil aggregates in Huntington's disease transgenic mice. Hum Mol Genet 1999, 8:1227-1236.
51. Li H, Li SH, Johnston H, Shelbourne PF, Li XJ: Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicity. Nat Genet 2000, 25:385-389.
52. Li H, Li SH, Yu ZX, Shelbourne P, Li XJ: Huntingtin aggregateassociated axonal degeneration is an early pathological event in Huntington's disease mice. J Neurosci 2001, 21:8473-8481.
53. Menalled LB, Sison JD, Dragatsis I, Zeitlin S, Chesselet MF: Time course of early motor and neuropathological anomalies in a knock-in mouse model of Huntington's disease with 140 CAG repeats. J Comp Neural 2003, 465:11-26.
54. Tallaksen-Greene SJ, Grouse AB, Hunter JM, Detloff PJ, Albin RL: Neuronal intranuclear inclusions and neuropil aggregates in HdhCAG(150) knockin mice. Neuroscience 2005, 131:843-852.
55. Hodgson JG, Agopyan N, Gutekunst CA, Leavitt BR, LePiane F, Singaraja R, Smith DJ, Bissada N, McCutcheon K, Nasir J, Jamot L, Li XJ, Stevens ME, Rosemond E, Roder JC, Phillips AG, Rubin EM, Hersch SM, Hayden MR: A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999, 23:181-192.
56. Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, Lu G, Pearson J, Shehadeh J, Bertram L, Murphy Z, Warby SC, Doty CN, Roy S, Wellington CL, Leavitt BR, Raymond LA, Nicholson DW, Hayden MR: Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 2006, 125:1179-1191.
57. Shelbourne PF, Killeen N, Hevner RF, Johnston HM, Tecott L, Lewandoski M, Ennis M, Ramirez L, Li Z, Iannicola C, Littman DR, Myers RM: 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.
58. Wheeler VC, White JK, Gutekunst CA, Vrbanac V, Weaver M, Li XJ, Li SH, Yi H, Vonsattel JP, Gusella JF, Hersch S, Auerbach W, Joyner AL, MacDonald ME: 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.
59. Menalled LB, Sison JD, Wu Y, Olivieri M, Li XJ, Li H, Zeitlin S, Chesselet MF: Early motor dysfunction and striosomal distribution of huntingtin microaggregates in Huntington's disease knock-in mice. J Neurasci 2002, 22:8266-8276.
60. Zhou H, Cao FL, Wang ZS, Yu ZX, Nguyen HP, Evans J, Li SH, Li XJ: Huntingtin forms toxic N-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity. J Cell Biol 2003 in press.
61. Kim YJ, Yi Y, Sapp E, Wang Y, Cuiffo B, Kegel KB, Qin ZH, 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 U S A 2001, 98:12784-12789.
62. Gafni J. Ellerby LM: Calpain activation in Huntington's disease. J Neurasci 2002, 22:4842-4849.
63. Wellington CL, Ellerby LM, Gutekunst CA, Rogers D, Warby S, Graham RK, Loubser O, van Raamsdonk J, Singaraja R, Yang YZ, Gafni J, Bredesen D, Hersch SM, Leavitt BR, Roy S, Nicholson DW, Hayden MR: Caspase cleavage of mutant huntingtin precedes neurodegeneration in Huntington's disease. J Neurosci 2002, 22:7862-7872.
64. Lunkes A, Lindenberg KS, Ben-Haiem L, Weber C, Devys D, Landwehrmeyer GB, Mandel JL, Trattier Y: Proteases acting on mutant huntingtin generate cleaved products that differentially build up cytoplasmic and nuclear inclusions. Mol Cell 2002, 10:259-269.
65. Hoogeveen AT, Willemsen R, Meyer N, de Rooij KE, Roos RA, van Ommen GJ, Galjaard H: Characterization and localization of the Huntington disease gene product. Hum Mol Genet 1993, 2:2069-2073.
66. Kegel KB, Meloni AR, Yi Y, Kim YJ, Doyle E, Cuiffo BG, Sapp E, Wang Y, Qin ZH, Chen JD, Nevins JR, 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.
67. Tanaka Y, Igarashi S, Nakamura M, Gafni J, Torcassi C, Schilling G, Crippen D, Wood JD, Sawa A, Jenkins NA, Copeland NG, Borchelt DR, Ross CA, Ellerby LM: Progressive phenotype and nuclear accumulation of an ammo-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin. Neurobiol Dis 2006, 21:381-391.
68. Schilling G, Savonenko AV, Klevytska A, Morton JL, Tucker SM, Poirier M, Gale A, Chan N, Gonzales V, Slunt HH, Coonfield ML, Jenkins NA, Copeland NG, Ross CA, Borchelt DR: Nuclear-targeting of mutant huntingtin fragments produces Huntington's disease-like phenotypes in transgenic mice. Hum Mol Genet 2004, 13:1599-1610.
69. Benn CL, Landles C, Li H, Strand AD, Woodman B, Sathasivam K, Li SH, Ghazi-Noori S, Hockly E, Faruque SM, Cha JH, Sharpe PT, Olson JM, Li XJ, Bates GP: Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease. Hum Mol Genet 2005, 14:3065-3078.
70. Cornett J, Cao F, Wang CE, Ross CA, Bates GP, Li SH, Li XJ: Polyglutamine expansion of huntingtin impairs its nuclear export. Nat Genet 2005, 37:198-204.
71. Sun Y, Savanenin A, Reddy PH, Liu YF: Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-D-aspartate receptors via post-synaptic density 95. J Biol Chem 2001, 276:24713-24718.
72. Hackam AS, Singaraja R, Wellington CL, Metzler M, McCutcheon K, Zhang T, Kalchman M, Hayden MR: The influence of huntingtin protein size on nuclear localization and cellular toxicity. J Cell Biol 1998, 141:1097-1 105.
73. Sugars KL, Rubinsztein DC: Transcriptional abnormalities in Huntington disease. Trends Genet 2003, 19:233-238.
74. Mantamadiotis T, Lemberger T, Bleckmann SC, 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.
75. Myers SJ, Dingledine R, Borges K: Genetic regulation of glutamate receptor ion channels. Annu Rev Pharmacol Toxicol 1999, 39:221-241.
76. Luthi-Carter R, Hanson SA, Strand AD, Bergstrom DA, Chun W, Peters NL, Woods AM, Chan EY, Kooperberg C, Krainc D, Young AB, Tapscott SJ, Olson JM: 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.
77. McCampbell A, Taylor JP, Taye AA, Robitschek J, Li M, Walcott J, Merry D, Chai Y, Paulson H, Sobue G, Fischbeck KH: CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet 2000, 9:2197-2202.
78. Chai Y, Wu L, Griffin JD, Paulson HL: The role of protein composition in specifying nuclear inclusion formation in polyglutamine disease, J Biol Chem 2001, 276:44889-44897.
79. Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M, Takahashi H, Tsuji S, Troncoso J, Dawson VL, Dawson TM, Ross CA: Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science 2001, 291:2423-2428.
80. Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, Kazantsev A, Schmidt E, Zhu YZ, Greenwald M, Kurokawa R, Housman DE, Jackson GR, Marsh JL, Thompson LM: Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001, 413:739-743.
81. Huang CC, Faber PW, Persichetti F, Mittal V, Vonsattel JP, MacDonald ME, Gusella JF: Amyloid formation by mutant huntingtin: threshold, progressivity and recruitment of normal polyglutamine proteins. Somat Cell Mol Genet 1998, 24:217-233.
82. Perez MK, Paulson HL, Pendse SJ, Saionz SJ, Bonini NM, Pittman RN: Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol 1998, 143:1457-1470.
83. 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: Expanded polyglutamine stretches interact with TAFII130, interfering with CREB-dependent transcription. Nat Genet 2000, 26:29-36.
84. Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PA, Steffan JS, Marsh JL, Thompson LM, Lewis CM, Marks PA, Bates GP: Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl Acad Sci U S A 2003, 100:2041-2046.
85. Yu ZX, Li SH, Nguyen HP, Li XJ: Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice. Hum Mol Genet 2002, 11:905-914.
86. Kita H, Carmichael J, Swartz J, Muro S, Wyttenbach A, Matsubara K, Rubinsztein DC, Kato K: Modulation of polyglutamine-induced cell death by genes identified by expression profiling. Hum Mol Genet 2002, 11:2279-2287.
87. Sipione S, Rigamonti D, Valenza M, Zuccato C, Conti L, Pritchard J, Kooperberg C, Olson JM, Cattaneo E: Early transcriptional profiles in huntingtin-inducible striatal cells by microarray analyses. Hum Mol Genet 2002, 11: 1953-1965.
88. Dunah AW, Jeong H, Griffin A, Kim YM, Standaert DG, Hersch SM, Mouradian MM, Young AB, Tanese N, Krainc D: Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease. Science 2002, 296:2238-2243.
89. Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ: Interaction of Huntington disease protein with transcriptional activator Sp1. Mol Cell Biol 2002, 22:1277-1287.
90. Schaffar G, Breuer P, Boteva R, Behrends C, Tzvetkov N, Strippel N, Sakahira H, Siegers K, Hayer-Hartl M, Hartl FU: Cellular toxicity of polyglutamine expansion proteins: mechanism of transcription factor deactivation. Mol Cell 2004, 15:95-105.
91. Bae Bl, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y, Hayward SD, Moran TH, Montell C, Ross CA, Snyder SH, Sawa A: p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005, 47:29-41.
92. Lin J, Wu PH, Tarr PT, Lindenberg KS, St-Pierre J, Zhang CY, Mootha VK, Jager S, Vianna CR, Reznick RM, Cui L, Manieri M, Donovan MX, Wu Z, Cooper MP, Fan MC, Rohas LM, Zavacki AM, Cinti S, Shulman Gl, Lowell BB, Krainc D, Spiegelman BM: Defects in adaptive energy metabolism with CNS-linked hyperactivity in PGCIalpha null mice. Cell 2004, 119:121-135.
93. St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM: Suppression of reactive oxygen species and neurodegeneration by the PGC-I transcriptional coactivators. Cell 2006, 127:397-408.
94. Cui L, Jeong H, Borovecki F, Parkhurst CN, Tanese N, Krainc D: Transcriptional repression of PGC-I alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration. Cell 2006, 127:59-69.
95. Weydt P, Pineda W, Torrence AE, Libby RT, Satterfield TF, Lazarowski ER, Gilbert ML, Morton GJ, Bammler TK, Strand AD, Cui L, Beyer RP, Easley CN, Smith AC, Krainc D, Luquet S, Sweet IR, Schwartz MW, La Spada AR: Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1 alpha in Huntington's disease neurodegeneration. Cell Metab 2006, 4:349-362.
96. Sanchez I, Xu CJ, Juo P, Kakizaka A, Blenis J, Yuan J: Caspase-8 is required for cell death induced by expanded polyglutamine repeats [see comments]. Neuron 1999, 22:623-633.
97. Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, Frey AS, Menon AS, Li XJ, Stieg PE, Yuan J, Penney JB, Young AB, Cha JH, Friedlander RM: Inhibition of caspase-l slows disease progression in a mouse model of Huntington's disease. Nature 1999, 399:263-267.
98. Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM: Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease. Nat Med 2000, 6:797-801.
99. Li SH, Lam S, Cheng AL, Li XJ: Intranuclear huntingtin increases the expression of caspase-1 and induces apoptosis. Hum Mol Genet 2000, 9:2859-2867.
100. Cepeda C, Ariano MA, Calvert CR, Flores-HernandezJ, Chandler SH, Leavitt BR, Hayden MR, Levine MS: NMDA receptor function in mouse models of Huntington disease. J Neurosci Res 2001, 66:525-539.
101. Song C, Perides G, Liu YF: Expression of full-length polyglutamine-expanded Huntingtin disrupts growth factor receptor signaling in rat pheochromocytoma (PC 12) cells. J Biol Chem 2002, 277:6703-6707.
102. Zeron MM, Hansson O, Chen N, Wellington CL, Leavitt BR, Brundin P, Hayden MR, Raymond LA: Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron 2002, 33:849-860.
103. Tang TS, Tu H, Chan EY, Maximov A, Wang Z, Wellington CL, Hayden MR. Bezprozvanny I: Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. Neuron 2003, 39:227-239.
104. Varani K, Rigamonti D, Sipione S, Camurri A, Borea PA, Cattabeni F, Abbracchio MP, Cattaneo E: Aberrant amplification of A(2A) receptor signaling in striatal cells expressing mutant huntingtin. Foseb J 2001, 15:1245-1247.
105. Borrell-Pages M, Zala D, Humbert S, Saudou F: Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell Mol Life Sci 2006, 63:2642-2660.
106. Li XJ, Li SH, Sharp AH, Nucifora FCJr, Schilling G, Lanahan A, Worley P, Snyder SH, Ross CA: A huntingtin-associated protein enriched in brain with implications for pathology. Nature 1995, 378:398-402.
107. Gauthier LR, Charrin BC, Borrell-Pages M, Dompierre JP, Rangone H, Cordelieres FP, De Mey J, MacDonald ME, 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.
108. Engelender S, Sharp AH, Colomer V, Tokito MK, Lanahan A, Worley P, Holzbaur EL, Ross CA: Huntingtin-associated protein 1 (HAPI) interacts with the p150Glued subunit of dynactin. Hum Mol Genet 1997, 6:2205-2212.
109. Li SH, Gutekunst CA, Hersch SM, Li XJ: Interaction of huntingtinassociated protein with dynactin P150Glued. J Neurose 1998, 18:1261-1269.
110. McGuire JR, Rong J, Li SH, Li XJ: Interaction of Huntingtin-associated protein-1 with kinesin light chain: implications in intracellular trafficking in neurons. J Biol Chem 2006, 281:3552-3559.
111. Li Y, Chin LS, Levey Al, Li L: Huntingtin-associated Protein 1 Interacts with Hepatocyte Growth Factor-regulated Tyrosine Kinase Substrate and Functions in Endosomal Trafficking. J Biol Chem 2002, 277:28212-28221.
112. Kittler JT, Thomas P, Tretter V, Bogdanov YD, Haucke V, Smart TG, Moss SJ: Huntingtin-associated protein I regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking. Proc Natl Acad Sci U S A 2004, 101:12736-12741.
113. Rong J, McGuire JR, Fang ZH, Sheng G, Shin JY, Li SH, Li XJ: Regulation of intracellular trafficking of huntingtin-associated protein-1 is critical for TrkA protein levels and neurite outgrowth, J Neurosci 2006, 26:6019-6030.
114. Chan EY, Nasir J, Gutekunst CA, Coleman S, Maclean A, Maas A, Metzler M, Gertsenstein M, Ross CA, Nagy A, Hayden MR: Targeted disruption of Huntingtin-associated protein-1 (HapI) results in postnatal death due to depressed feeding behavior. Hum Mol Genet 2002, 11:945-959.
115. Li SH, Yu ZX, Li CL, Nguyen HP, Zhou YX, Deng C, Li XJ: Lack of huntingtin-associated protein-1 causes neuronal death resembling hypothalamic degeneration in Huntington's disease. J Neurose J 2003, 23:6956-6964.
116. Sheng G, Chang GQ, Lin JY, Yu ZX, Fang ZH, Kong J, Lipton SA, Li SH, Tong G, Leibowitz SF, Li XJ: Hypothalamic huntingtin-associated protein 1 as a mediator of feeding behavior. Nat Med 2006, 12:526-533.
117. Petersen A, Gil J, Maat-Schieman ML, Bjorkqvist M, Tanila H, Araujo IM, Smith R, Popovic N. Wierup N, Norlen P, Li JY, Roos RA, Sundler F, Mulder H, Brundin P: Orexin loss in Huntington's disease. Hum Mol Genet 2005, 14:39-47.
118. Kalchman MA, Koide HB, McCutcheon K, Graham RK, Nichol K, Nishiyama K, Kazemi-Esfarjani P, Lynn FC, Wellington C, Metzler M, Goldberg YP, Kanazawa I, Gietz RD, Hayden MR: HIPI, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat Genet 1997, 16:44-53.
119. Metzler M, Li B, Gan L, Georgiou J, Gutekunst CA, Wang Y, Torre E, Devon RS, Oh R, Legendre-Guillemin V, Rich M, Alvarez C, Gertsenstein M, McPherson PS, Nagy A, Wang YT, Roder JC, Raymond LA, Hayden MR: Disruption of the endocytic protein HIPI results in neurological deficits and decreased AMPA receptor trafficking. Embo J 2003, 22:3254-3266.
120. Mishra SK, Agostinelli NR, Brett TJ, Mizukami I, Ross TS, Traub LM: Clathrin- and AP-2-binding sites in HIPI uncover a general assembly role for endocytic accessory proteins, J Biol Chern 2001, 276:46230- 46236.
121. Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE: The huntingtin interacting protein HIPI is a clathrin and alphaadaptin-binding protein involved in receptor-mediated endocytosis. Hum Mol Genet 2001, 10:1807-1817.
122. Gunawardena S, Her LS, Brusch RG, Laymon RA, Niesman IR, Gordesky-Gold B, Sintasath L, Bonini NM, Goldstein LS: Disruption of axonal transport by loss of huntingtin or expression of pathogenic polyQ proteins in Drosophila. Neuron 2003, 40:25-40.
123. Trushina E, Dyer RB, Badger JD 2nd, Ure D, Eide L, Tran DD, Vrieze BT, Legendre-Guillemin V, McPherson PS, Mandavilli BS, Van Houten B, Zeitlin S, McNiven M, Aebersold R, Hayden M, Parisi JE, Seeberg E, Dragatsis 1, Doyle K, Bender A, Chacko C, McMurray CT: Mutant huntingtin impairs axonal trafficking in Mammalian neurons in vivo and in vitro. Mol Cell Biol 2004, 24:8195-8209.
124. Parker JA, Connolly JB, 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 U S A 2001, 98:13318-13323.
125. Szebenyi G, Morfini GA, Babcock A, Gould M, Selkoe K, Stenoien DL, Young M, Faber PW, MacDonald ME, McPhaul MJ, Brady ST: Neuropathogenic forms of huntingtin and androgen receptor inhibit fast axonal transport. Neuron 2003, 40:41-52.
126. Li H, Wyman T, Yu ZX, Li SH, Li XJ: Abnormal association of mutant huntingtin with synaptic vesicles inhibits glutamate release. Hum Mol Genet 2003, 12:2021-2030.
127. Li XJ, Li SH: HAPI and intracellular trafficking. Trends Pharmacol Sci 2005, 26:1-3.
128. Chang DT, Rintoul GL, Pandipati S, Reynolds IJ: Mutant huntingtin aggregates impair mitochondrial movement and trafficking in cortical neurons. Neurobiol Dis 2006, 22:388-400.
129. Lee WC, Yoshihara M, Littleton JT: Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal transport in a Drosophila model of Huntington's disease. Proc Natl Acad Sci U S A 2004, 101:3224-3229.
130. Coleman MP, Perry VH: Axon pathology in neurological disease: a neglected therapeutic target. Trends Neurosci 2002, 25:532-537.
131. Raff MC, Whitmore AV, Finn JT: Axonal self-destruction and neurodegeneration. Science 2002, 296:868-871.
132. Rothstein JD, Dykes-Hoberg M, Pardo CA, Bristol LA, Jin L, Kuncl RW, Kanai Y, Hediger MA, Wang Y, Schielke JP, Welty DF: Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 1996, 16:675-686.
133. Ridet JL, Malhotra SK, Privat A, Gage FH: Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 1997, 20:570-577.
134. Fields RD, Stevens-Graham B: New insights into neuron-glia communication. Science 2002, 298:556-562.
135. Beal MF: Huntington's disease, energy, and excitotoxicity. Neurobiol Aging 1994, 15:275-276.
136. Coyle JT, Schwarcz R: Lesion of striatal neurones with kainic acid provides a model for Huntington's chorea. Nature 1976, 263:244-246.
137. DiFiglia M: Excitotoxic injury of the neostriatum: a model for Huntington's disease. Trends Neurosci 1990, 13:286-289.
138. Choi DW: Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988, 1:623-634.
139. Hantraye P, Riche D, Maziere M, Isacson O: A primate model of Huntington's disease: behavioral and anatomical studies of unilateral excitotoxic lesions of the caudate-putamen in the baboon. Exp Neural 1990, 108:91-104.
140. Greene JG, Porter RH, Eller RV, Greenamyre JT: Inhibition of succinate dehydrogenase by malonic acid produces an "excitotoxic" lesion in rat striatum. J Neurochem 1993, 61:1151-1154.
141. Levine MS, Klapstein GJ, Koppel A, Gruen E, Cepeda C, Vargas ME, Jokel ES, Carpenter EM, Zanjani H, Hurst RS, Efstratiadis A, Zeitlin S, Chesselet MF: 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.
142. Laforet GA, Sapp E, Chase K, McIntyre C, Boyce FM, Campbell M, Cadigan BA, Warzecki L, Tagle DA, Reddy PH, Cepeda C, Calvert CR, Jokel ES, Klapstein GJ, Ariano MA, Levine MS, 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.
143. Maragakis NJ, Rothstein JD: Glutamate transporters in neurologic disease. Arch Neural 2001, 58:365-370.
144. Lievens JC, Woodman B, Mahal A, Spasic-Boscovic O, Samuel D, Kerkerian-Le Goff L, Bates GP: Impaired glutamate uptake in the R6 Huntington's disease transgenic mice. Neurobiol Dis 2001, 8:807-821.
145. Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB: Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Brain 2002, 125:1908-1922.
146. Lievens JC, Rival T, Iche M, Chneiweiss H, Birman S: Expanded polyglutamine peptides disrupt EGF receptor signaling and glutamate transporter expression in Drosophila. Hum Mol Genet 2005, 14:713-724.
147. Shin JY, Fang ZH, Yu ZX, Wang CE, Li SH, Li XJ: Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity. J Cell Biol 2005, 171:1001-1012.