Molecular basis of Huntington's disease and possible pathogenic mechanisms;Bases moleculares de la enfermedad de Huntington y posibles mecanismos patogénicos

Revista de Neurologia

Volumn 35, Issue 3, 2002, Pages 212-220

  Martin Aparicio E ^a   Lucas, José Javier ^a  

^a UNIVERSIDAD AUTÓNOMA DE MADRID   (Spain)

Author keywords

Aggregates; Basal ganglia; Huntington's disease; Neuropathology; Poly glutamines; Striatum

Indexed keywords

ADENINE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN BINDING PROTEIN; CYTOSINE; GLUTAMINE; GUANINE; TATA BINDING PROTEIN;

AMINO ACID SEQUENCE; BASAL GANGLION; BRAIN CORTEX; CHOREA; COGNITIVE DEFECT; CORPUS STRIATUM; GENE MUTATION; GLIOSIS; HUMAN; HUNTINGTON CHOREA; MUSCLE RIGIDITY; NEUROPATHOLOGY; PATHOGENESIS; PROTEIN AGGREGATION; REVIEW; SYMPTOMATOLOGY;

EID: 0036704903     PISSN: 02100010     EISSN: None     Source Type: Journal    
DOI: 10.33588/rn.3503.2002339     Document Type: Review

References (158)

1. Wexler NS, Young AB, Tanzi RE, Travers H, Starosta-Rubinstein S, Penney JB, et al. Homozygotes for Huntington's disease. Nature 1987; 326: 194-7.
2. Ambrose CM, Duyao MP, Barnes G, Bates GP, Lin CS, Srinidhi J, et al. Structure and expression of the Huntington's disease gene: Evidence against simple inactivation due to an expanded CAG repeat. Somat Cell Mol Genet 1994; 20: 27-38.
3. Craufurd D, Dodge A. Mutation size and age at onset in Huntington's disease. J Med Genet 1993; 30: 1008-11.
4. Foroud T, Gray J, Ivashina J, Conneally PM. Differences in duration of Huntington's disease based on age at onset. J Neurol Neurosurg Psychiatry 1999; 66: 52-6.
5. Holthoff VA, Koeppe RA, Frey KA, Penney JB, Markel DS, Kuhl DE, et al. Positron emission tomography measures of benzodiazepine receptors in Huntington's disease. Ann Neurol 1993; 34: 76-81.
6. Kuwert T, Noth J, Scholz D, Schwarz M, Lange HW, Topper R, et al. Comparison of somatosensory evoked potentials with striatal glucose consumption measured by positron emission tomography in the early diagnosis of Huntington's disease. Mov Disord 1993; 8: 98-106.
7. De Boo GM, Tibben A, Lanser JB, Jennekens-Schinkel A, Hermans J, Maat-Kievit A, et al. Early cognitive and motor symptoms in identified carriers of the gene for Huntington disease. Arch Neurol 1997; 54: 1353-7.
8. Berardelli A, Noth J, Thompson PD, Bollen EL, Curra A, Deuschl G, et al. Pathophysiology of chorea and bradykinesia in Huntington's disease. Mov Disord 1999; 14: 398-403.
9. Van Vugt JP, Siesling S, Piet KK, Zwinderman AH, Middelkoop HA, Van Hilten JJ, et al. Quantitative assessment of daytime motor activity provides a responsive measure of functional decline in patients with Huntington's disease. Mov Disord 2001; 16: 481-8.
10. Leopold NA, Kagel MC. Dysphagia in Huntington's disease. Arch Neurol 1985; 42: 57-60.
11. Rosenblatt A, Leroi I. Neuropsychiatry of Huntington's disease and other basal ganglia disorders. Psychosomatics 2000; 41: 24-30.
12. Haddad MS, Cummings JL. Huntington's disease. Psychiatr Clin North Am 1997; 20: 791-807.
13. Pratley RE, Salbe AD, Ravussin E, Caviness JN. Higher sedentary energy expenditure in patients with Huntington's disease. Ann Neurol 2000; 47: 64-70.
14. Srivastava T, Lal V, Prabhakar S. Juvenile Huntington's disease [letter]. Neurol India 1999; 47: 340-1.
15. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 1985; 44: 559-77.
16. Afifi AK. Basal ganglia: Functional anatomy and physiology. Part 2. J Child Neurol 1994; 9: 352-61.
17. DiFiglia M, Sapp E, Chase K, Davies S, Bates G, Vonsattel J, et al. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 1997; 277: 1990-3.
18. Lange H, Thorner G, Hopf A, Schroder KF. Morphometric studies of the neuropathological changes in choreatic diseases. J Neurol Sci 1976; 28: 401-25.
19. Graybiel AM, Aosaki T, Flaherty AW, Kimura M. The basal ganglia and adaptive motor control. Science 1994; 265: 1826-31.
20. Flaherty AW, Graybiel AM. Output architecture of the primate putamen. J Neurosci 1993; 13: 3222-37.
21. Strange PG. New insights into dopamine receptors in the central nervous system. Neurochem Int 1993; 22: 223-36.
22. Gerfen CR. Synaptic organization of the striatum. J Electron Microsc Tech 1988; 10: 265-81.
23. Gerfen CR. The neostriatal mosaic: Multiple levels of compartmental organization. Trends Neurosci 1992; 15: 133-9.
24. Reiner A, Albin RL, Anderson KD, D'Amato CJ, Penney JB, Young AB. Differential loss of striatal projection neurons in Huntington disease. Proc Natl Acad Sci U S A 1988; 85: 5733-7.
25. Sotrel A, Williams RS, Kaufmann WE, Myers RH. Evidence for neuronal degeneration and dendritic plasticity in cortical pyramidal neurons of Huntington's disease: A quantitative Golgi study. Neurology 1993; 43: 2088-96.
26. Maat-Schieman ML, Dorsman JC, Smoor MA, Siesling S, Van Duinen SG, Verschuuren JJ, et al. Distribution of inclusions in neuronal nuclei and dystrophic neurites in Huntington disease brain. J Neuropathol Exp Neurol 1999; 58: 129-37.
27. Sieradzan KA, Mechan AO, Jones L, Wanker EE, Nukina N, Mann DM. Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp Neurol 1999; 156: 92-9.
28. Gutekunst CA, Li SH, Yi H, Mulroy JS, Kuemmerle S, Jones R, et al. Nuclear and neuropil aggregates in Huntington's disease: Relationship to neuropathology. J Neurosci 1999; 19: 2522-34.
29. The Huntington's Disease Collaborative Research Group. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 1993; 72: 971-83.
30. Rubinsztein DC, Amos W, Leggo J, Goodbum S, Ramesar RS, Old J, et al. Mutational bias provides a model for the evolution of Huntington's disease and predicts a general increase in disease prevalence. Nat Genet 1994; 7: 525-30.
31. Gusella JF, MacDonald ME. Trinucleotide instability: A repeating theme in human inherited disorders. Annu Rev Med 1996; 47: 201-9.
32. Andrew SE, Goldberg YP, Kremer B, Telenius H, Theilmann J, Adam S, et al. The relationship between trinucleotide (CAG) repeat length and clinical features of Huntington's disease. Nat Genet 1993; 4: 398-403.
33. Evert BO, Wullner U, Klockgether T. Cell death in polyglutamine diseases. Cell Tissue Res 2000; 301: 189-204.
34. Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, et al. SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Hum Mol Genet 2001; 10: 1441-8.
35. Ross CA. Intranuclear neuronal inclusions: A common pathogenic mechanism for glutamine-repeat neurodegenerative diseases? Neuron 1997; 19: 1147-50.
36. Becher MW, Kotzuk JA, Sharp AH, Davies SW, Bates GP, Price DL, et al. 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: 387-97.
37. Holmberg M, Duyckaerts C, Durr A, Cancel G, Gourfinkel-An I, Damier P, et al. Spinocerebellar ataxia type 7 (SCAT): A neurodegenevative disorder with neuronal intranuclear inclusions. Hum Mol Genet 1998; 7: 913-8.
38. Li M, Miwa S, Kobayashi Y, Merry DE, Yamamoto M, Tanaka F, et al. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol 1998; 44: 249-54.
39. Lieberman AP, Trojanowski JQ, Leonard DG, Chen KL, Barnett JL, Leverenz JB, et al. Ataxin 1 and ataxin 3 in neuronal intranuclear inclusion disease. Ann Neurol 1999; 46: 271-3.
40. Paulson HL, Perez MK, Trottier Y, Trojanowski JQ, Subramony SH, Das SS, et al. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron 1997; 19: 333-44.
41. Skinner P, Koshy B, Cummings C, Klement I, Helin K, Servasio A, et al. Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures. Nature 1997; 389: 971-4.
42. Li SH, Schilling G, Young WSd, Li XJ, Margolis RL, Stine OC, et al. Huntington's disease gene (IT 15) is widely expressed in human and rat tissues. Neuron 1993; 11: 985-93.
43. DiFiglia M, Sapp E, Chase K, Schwarz C, Meloni A, Young C, et al. Huntingtin is a cytoplasmic protein associated with vesicles in human and rat brain neurons. Neuron 1995; 14: 1075-81.
44. Sharp AH, Loev SJ, Schilling G, Li SH, Li XJ, Bao J, et al. Widespread expression of Huntington's disease gene (IT 15) protein product. Neuron 1995; 14: 1065-74.
45. Bhide PG, Day M, Sapp E, Schwarz C, Sheth A, Kim J, et al. Expression of normal and mutant huntingtin in the developing brain. J Neurosci 1996; 16: 5523-35.
46. Gourfinkel-An I, Cancel G, Trottier Y, Devys D, Tora L, Lutz Y, et al. Differential distribution of the normal and mutated forms of huntingtin in the human brain. Ann Neurol 1997; 42: 712-9.
47. Landwehrmeyer GB, McNeil SM, Dure LSt, Ge P, Aizawa H, Huang Q, et al. Huntington's disease gene: Regional and cellular expression in brain of normal and affected individuals. Ann Neurol 1995; 37: 218-30.
48. Sapp E, Schwarz C, Chase K, Bhide PG, Young AB, Penney J, et al. Huntingtin localization in brains of normal and Huntington's disease patients. Ann Neurol 1997; 42: 604-12.
49. Tukamoto T, Nukina N, Ide K, Kanazawa I. Huntington's disease gene product, huntingtin, associates with microtubules in vitro. Brain Res Mol Brain Res 1997; 51: 8-14.
50. Gutekunst CA, Levey AI, Heilman CJ, Whaley WL, Yi H, Nash NR, et al. Identification and localization of huntingtin in brain and human lymphoblastoid cell lines with anti-fusion protein antibodies. Proc Natl Acad Sci U S A 1995; 92: 8710-4.
51. Velier J, Kim M, Schwarz C, Kim TW, Sapp E, Chase K, et al. Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways. Exp Neurol 1998; 152: 34-40.
52. 1 receptor activation increase huntingtin's association with endosomes in immortalized neuronal cells of striatal origin. Neuroscience 1999; 89: 1159-67.
53. Fenante RJ, Gutekunst CA, Persichetti F, McNeil SM, Kowall NW, Gusella JF, et al. Heterogeneous topographic and cellular distribution of huntingtin expression in the normal human neostriatum. J Neurosci 1997; 17: 3052-63.
54. Fusco FR, Chen Q, Lamoreaux WJ, Figueredo-Cardenas G, Jiao Y, Coffman JA, et al. Cellular localization of huntingtin in striatal and cortical neurons in rats: Lack of correlation with neuronal vulnerability in Huntington's disease. J Neurosci 1999; 19: 1189-202.
55. Duyao MP, Auerbach AB, Ryan A, Persichetti F, Barnes GT, McNeil SM, et al. Inactivation of the mouse Huntington's disease gene homolog Hdh. Science 1995; 269: 407-10.
56. Nasir J, Floresco SB, O'Kusky JR, Diewert VM, Richman JM, Zeisler J, et al. Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 1995; 81: 811-23.
57. 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: 155-63.
58. Bao J, Sharp AH, Wagster MV, Becher M, Schilling G, Ross CA, et al. Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. Proc Natl Acad Sci U S A 1996; 93: 5037-42.
59. Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H, et al. The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc Natl Acad Sci U S A 2000; 97: 6763-8.
60. Boutell JM, Wood JD, Harper PS, Jones AL. Huntingtin interacts with cystathionine beta-synthase. Hum Mol Genet 1998; 7: 371-8.
61. Burke JR, Enghild JJ, Martin ME, Jou YS, Myers RM, Roses AD, et al. Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nat Med 1996; 2: 347-50.
62. Liu YF, Deth RC, Devys D. SH3 domain-dependent association of huntingtin with epidermal growth factor receptor signaling complexes. J Biol Chem 1997; 272: 8121-4.
63. Peters MF, Ross CA. Isolation of a 40 kDa huntingtin-associated protein. J Biol Chem 2000.
64. Liu YF, Dorow D, Marshall J. Activation of MLK2-mediated signaling cascades by polyglutamine-expanded huntingtin. J Biol Chem 2000; 275:19035-40.
65. Boutell JM, Thomas P, Neal JW, Weston VJ, Duce J, Harper PS, et al. Aberrant interactions of transcriptional repressor proteins with the Huntington's disease gene product, huntingtin. Hum Mol Genet 1999; 8: 1647-55.
66. Li XJ, Li SH, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A, et al. A huntingtin-associated protein enriched in brain with implications for pathology. Nature 1995; 378: 398-402.
67. Block-Galarza J, Chase KO, Sapp E, Vaughn KT, Vallee RB, DiFiglia M, et al. Fast transport and retrograde movement of huntingtin and HAP1 in axons. Neuroreport 1997; 8: 2247-51.
68. Wanker EE, Rovira C, Scherzinger E, Hasenbank R, Walter S, Tait D, et al. HIP-I: A huntingtin interacting protein isolated by the yeast two-hybrid system. Hum Mol Genet 1997; 6: 487-95.
69. Kalchman MA, Koide HB, McCutcheon K, Graham RK, Nichol K, Nishiyama K, et al. HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain. Nat Genet 1997; 16: 44-53.
70. Gusella JF, MacDonald ME. Huntingtin: A single bait hooks many species. Curr Opin Neurobiol 1998; 8: 425-30.
71. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, et al. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet 1996; 13:442-9.
72. Durr A, Hahn-Barma V, Brice A, Pecheux C, Dode C, Feingold J. Homozygosity in Huntington's disease [letter]. J Med Genet 1999; 36: 172-3.
73. Zoghbi HY, Orr HT. Glutamine repeats and neurodegeneration. Annu Rev Neurosci 2000; 23: 217-47.
74. Ordway JM, Tallaksen-Greene S, Gutekunst CA, Bernstein EM, Cearley JA, Wiener HW, et al. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 1997; 91: 753-63.
75. Metzler M, Chen N, Helgason CD, Graham RK, Nichol K, McCutcheon K, et al. Life without huntingtin: Normal differentiation into functional neurons. J Neurochem 1999; 72: 1009-18.
76. White JK, Auerbach W, Duyao MP, Vonsattel JP, Gusella JF, Joyner AL, et al. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat Genet 1997; 17: 404-10.
77. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, et al. 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.
78. Yamamoto A, Lucas JJ, Hen R. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 2000; 101: 57-66.
79. 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: 182-8.
80. 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: 300-6.
81. Hodgson JG, Agopyan N, Gutekunst CA, Leavitt BR, LePiane F, Singaraja R, et al. A YAC mouse model for Huntington's disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 1999; 23: 181-92.
82. Reddy PH, Williams M, Charles V, Garrett L, Pike-Buchanan L, Whetsell WO Jr, et al. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet 1998; 20: 198-202.
83. Leavitt BR, Guttman JA, Hodgson JG, Kimel GH, Singaraja R, Vogl AW, et al. Wild-type huntingtin reduces the cellular toxicity of mutant huntingtin in vivo. Am J Hum Genet 2001; 68: 313-24.
84. Hackam AS, Yassa AS, Singaraja R, Metzler M, Gutekunst CA, Gan L, et al. Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain. J Biol Chem 2000; 275: 41299-308.
85. Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME. Huntingtin interacts with a family of WW domain proteins. Hum Mol Genet 1998; 7: 1463-74.
86. Rigamonti D, Bauer JH, De-Fraja C, Conti L, Sipione S, Sciorati C, et al. Wild-type huntingtin protects from apoptosis upstream of caspase-3. J Neurosci 2000; 20: 3705-13.
87. Zuccato C, Ciammola A, Rigamonti D, Leavitt BR, Goffredo D, Conti L, et al. Loss of huntingtin-mediated BDNF gene transcription in Huntington's disease. Science 2001; 14: 14.
88. Wheeler VC, White JK, Gutekunst CA, Vrbanac V, Weaver M, Li XJ, et al. 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: 503-13.
89. Courey AJ, Holtzman DA, Jackson SP, Tjian R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell 1989; 59: 827-36.
90. Gerber HP, Seipel K, Georgiev O, Hofferer M, Hug M, Rusconi S, et al. Transcriptional activation modulated by homopolymeric glutamine and proline stretches. Science 1994; 263: 808-11.
91. Cha JH. Transcriptional dysregulation in Huntington's disease. Trends Neurosci 2000; 23: 387-92.
92. Huang CC, Faber PW, Persichetti F, Mittal V, Vonsattel JP, MacDonald ME, et al. Amyloid formation by mutant huntingtin: Threshold, progressivity and recruitment of normal polyglutamine proteins. Somat Cell Mol Genet 1998; 24: 217-33.
93. Andrade MA, Bork P. HEAT repeats in the Huntington's disease protein. Nat Genet 1995; 11: 115-6.
94. Vetter IR, Arndt A, Kutay U, Gorlich D, Wittinghofer A. Structural view of the Ran-Importin beta interaction at 2.3 A resolution. Cell 1999; 97: 635-46.
95. 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.
96. Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M, et al. Interference by huntingtin and atrophin-1 with CBP-mediated transcription leading to cellular toxicity. Science 2001; 291: 2423-8.
97. Steffan JS, Bodai L, Pallos J, Poelman M, McCampbell A, Apostol BL, et al. Historic deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila. Nature 2001; 413: 739-43.
98. McCampbell A, Taye AA, Whitty L, Penney E, Steffan JS, Fischbeck KH. Histone deacetylase inhibitors reduce polyglutamine toxicity. Proc Natl Acad Sci U S A 2001; 98: 15179-84.
99. Passani LA, Bedford MT, Faber PW, McGinnis KM, Sharp AH, Gusella JF, et al. Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis. Hum Mol Genet 2000; 9: 2175-82.
100. Li SH, Cheng AL, Li H, Li XJ. Cellular defects and altered gene expression in PC12 cells stably expressing mutant huntingtin. J Neurosci 1999; 19: 5159-72.
101. Cha JH, Frey AS, Alsdorf SA, Kerner JA, Kosinski CM, Mangiarini L, et al. Altered neurotransmitter receptor expression in transgenic mouse models of Huntington's disease. Philos Trans R Soc Lond B Biol Sci 1999; 354: 981-9.
102. Cha JH, Kosinski CM, Kemer JA, Alsdorf SA, Mangiarini L, Davies SW, et al. Altered brain neurotransmitter receptors in transgenic mice expressing a portion of an abnormal human huntington disease gene. Proc Natl Acad Sci U S A 1998; 95: 6480-5.
103. Luthi-Carter R, Strand A, Peters NL, Solano SM, Hollingsworth ZR, Menon AS, et al. Decreased expression of striatal signaling genes in a mouse model of Huntington's disease. Hum Mol Genet 2000; 9: 1259-71.
104. Sittler A, Walter S, Wedemeyer N, Hasenbank R, Scherzinger E, Eickhoff H, et al. SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates. Mol Cell 1998; 2: 427-36.
105. 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: 385-9.
106. Kegel KB, Kim M, Sapp E, McIntyre C, Castano JG, Aronin N, et al. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci 2000; 20: 7268-78.
107. Gu M, Gash MT, Mann VM, Javoy-Agid F, Cooper JM, Schapira AH. Mitochondrial defect in Huntington's disease caudate nucleus. Ann Neurol 1996; 39: 385-9.
108. Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, et al. Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia. Ann Neurol 1997; 41: 646-53.
109. Tabrizi SJ, Cleeter MW, Xuereb J, Taanman JW, Cooper JM, Schapira AH. Biochemical abnormalities and excitotoxicity in Huntington's disease brain. Ann Neurol 1999; 45: 25-32.
110. Koroshetz WJ, Jenkins BG, Rosen BR, Beal MF. Energy metabolism defects in Huntington's disease and effects of coenzyme Q10. Ann Neurol 1997; 41: 160-5.
111. Arenas J, Campos Y, Ribacoba R, Martin MA, Rubio JC, Ablanedo P, et al. Complex I defect in muscle from patients with Huntington's disease. Ann Neurol 1998; 43: 397-400.
112. Tabrizi SJ, Workman J, Hart PE, Mangiarini L, Mahal A, Bates G, et al. Mitochondrial dysfunction and free radical damage in the Huntington R6/2 transgenic mouse. Ann Neurol 2000; 47: 80-6.
113. Hackam AS, Singaraja R, Wellington CL, Metzler M, McCutcheon K, Zhang T, et al. The influence of huntingtin protein size on nuclear localization and cellular toxicity. J Cell Biol 1998; 141: 1097-105.
114. O'Kusky JR, Nasir J, Cicchetti F, Parent A, Hayden MR. Neuronal degeneration in the basal ganglia and loss of pallido-subthalamic synapses in mice with targeted disruption of the Huntington's disease gene. Brain Res 1999; 818: 468-79.
115. Kim M, Lee HS, LaForet G, McIntyre C, Martin EJ, Chang P, et al. Mutant huntingtin expression in clonal striatal cells: Dissociation of inclusion formation and neuronal survival by caspase inhibition. J Neurosci 1999; 19: 964-73.
116. Sanchez I, Xu CJ, Juo P, Kakizaka A, Blenis J, Yuan J. Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron 1999; 22: 623-33.
117. Wellington CL, Singaraja R, Ellerby L, Savill J, Roy S, Leavitt B, et al. Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J Biol Chem 2000; 275: 19831-8.
118. Wellington CL, Ellerby LM, Hackam AS, Margolis RL, Trifiro MA, Singaraja R, et al. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem 1998; 273: 9158-67.
119. Goldberg YP, Nicholson DW, Rasper DM, Kalchman MA, Koide HB, Graham RK, et al. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet 1996; 13: 442-9.
120. Ona VO, Li M, Vonsattel JP, Andrews LJ, Khan SQ, Chung WM, et al. Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's disease. Nature 1999; 399: 263-7.
121. Turmaine M, Raza A, Mahal A, Mangiarini L, Bates GP, Davies SW. Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease. Proc Natl Acad Sci U S A 2000; 97: 8093-7.
122. Graveland GA, Williams RS, DiFiglia M. Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington's disease. Science 1985; 227: 770-3.
123. Zeron MM, Hansson O, Chen N, Wellington CL, Leavitt BR, Brundin P, et al. Increased sensitivity to N-methyl-D-aspartate receptor-mediated excitotoxicity in a mouse model of Huntington's disease. Neuron 2002; 33: 849-60.
124. 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: 24713-8.
125. Levine MS, Klapstein GJ, Koppel A, Gruen E, Cepeda C, Vargas ME, et al. Enhanced sensitivity to N-methyl-D-aspartate receptor activation in transgenic and knockin mouse models of Huntington's disease. J Neurosci Res 1999; 58: 515-32.
126. Bibb JA, Yan Z, Svenningsson P, Snyder GL, Pieribone VA, Horiuchi A, et al. Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice. Proc Natl Acad Sci U S A 2000; 97: 6809-14.
127. Klapstein GJ, Fisher RS, Zanjani H, Cepeda C, Jokel ES, Chesselet MF, et al. Electrophysiological and morphological changes in striatal spiny neurons in R6/2 Huntington's disease transgenic mice. J Neurophysiol 2001; 86: 2667-77.
128. Murphy KP, Carter RJ, Lione LA, Mangiarini L, Mahal A, Bates GP, et al. Abnormal synaptic plasticity and impaired spatial cognition in mice transgenic for exon 1 of the human Huntington's disease mutation. J Neurosci 2000; 20: 5115-23.
129. Usdin MT, Shelbourne PF, Myers RM, Madison DV. Impaired synaptic plasticity in mice carrying the Huntington's disease mutation. Hum Mol Genet 1999; 8: 839-46.
130. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, et al. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 1997; 90: 549-58.
131. Cooper JK, Schilling G, Peters MF, Herring WJ, Sharp AH, Kaminsky Z, et al. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet 1998; 7: 783-90.
132. Li SH, Li XJ. Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats. Hum Mol Genet 1998; 7: 777-82.
133. Martindale D, Hackam A, Wieczorek A, Ellerby L, Wellington C, McCutcheon K, et al. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet 1998; 18: 150-4.
134. Krobitsch S, Lindquist S. Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc Natl Acad Sci U S A 2000; 97: 1589-94.
135. Peters MF, Nucifora FC Jr, Kushi J, Seaman HC, Cooper JK, Herring WJ, et al. Nuclear targeting of mutant huntingtin increases toxicity. Mol Cell Neurosci 1999; 14: 121-8.
136. Lunkes A, Mandel JL. A cellular model that recapitulates major pathogenic steps of Huntington's disease. Hum Mol Genet 1998; 7: 1355-61.
137. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, et al. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 1997; 90: 537-48.
138. Schilling G, Becher MW, Sharp AH, Jinnah HA, Duan K, Kotzuk JA, et al. Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin. Hum Mol Genet 1999; 8: 397-407.
139. Shelbourne PF, Killeen N, Hevner RF, Johnston HM, Tecott L, Lewandoski M, et al. 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: 763-74.
140. Kahlem P, Green H, Djian P. Transglutaminase as the agent of neurodegenerative diseases due to polyglutamine expansion. Pathol Biol (Paris) 1998; 46: 681-2.
141. Kahlem P, Green H, Djian P. Transglutaminase action imitates Huntington's disease: Selective polymerization of Huntingtin containing expanded polyglutamine. Mol Cell 1998; 1: 595-601.
142. Karpuj MV, Garren H, Slunt H, Price DL, Gusella J, Becher MW, et al. Transglutaminase aggregates huntingtin into nonamyloidogenic polymers, and its enzymatic activity increases in Huntington's disease brain nuclei. Proc Natl Acad Sci U S A 1999; 96: 7388-93.
143. Lesort M, Chun W, Johnson GV, Ferrante RJ. Tissue transglutaminase is increased in Huntington's disease brain. J Neurochem 1999; 73: 2018-27.
144. Perutz MF, Johnson T, Suzuki M, Finch JT. Glutamine repeats as polar zippers: Their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci U S A 1994; 91: 5355-8.
145. Perutz MF. Glutamine repeats and inherited neurodegenerative diseases: Molecular aspects. Curr Opin Struct Biol 1996; 6: 848-58.
146. Martín-Aparicio E, Yamamoto A, Henández F, Hen R, Ávila J, Lucas JJ. Proteasomal-dependent aggregate reversal and absence of cell death in a conditional mouse model of Huntington's disease. J Neurosci 2001; 21: 8772-81.
147. Price DL, Sisodia SS, Borchelt DR. Genetic neurodegenerative diseases: The human illness and transgenic models. Science 1998; 282: 1079-83.
148. Tobin AJ, Signer ER. Huntington's disease: The challenge for cell biologists. Trends Cell Biol 2000; 10: 531-6.
149. Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, Lehrach H, et al. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 2001; 12: 1393-407.
150. Leavitt BR, Wellington CL, Hayden MR. Recent insights into the molecular pathogenesis of Huntington disease. Semin Neurol 1999; 19: 385-95.
151. Klement IA, Skinner PJ, Kaytor MD, Yi H, Hersch SM, Clark HB, et al. Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 1998; 95: 41-53.
152. Cummings CJ, Reinstein E, Sun Y, Antalffy B, Jiang Y, Ciechanover A, et al. Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 mice. Neuron 1999; 24: 879-92.
153. Wyttenbach A, Carmichael J, Swartz J, Furlong RA, Narain Y, Rankin J, et al. 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 U S A 2000; 97: 2898-903.
154. Scherzinger E, Sittler A, Schweiger K, Heiser V, Lurz R, Hasenbank R, et al. Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington's disease pathology. Proc Natl Acad Sci U S A 1999; 96: 4604-9.
155. Jana NR, Zemskov EA, 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: 1049-59.
156. Bence NF, Sampat RM, Kopito RR. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 2001; 292: 1552-5.
157. Gelman MS, Kannegaard ES, Kopito RR. A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator. J Biol Chem 2002; 277: 11709-14.
158. Ding Q, Lewis JJ, Strum KM, Dimayuga E, Bruce-Keller AJ, Dunn JC, et al. Polyglutamine expansion, protein aggregation, proteasome activity, and neural survival. J Biol Chem 2002; 277: 13935-42.