Huntington's disease

Cold Spring Harbor Perspectives in Biology

Volumn 3, Issue 6, 2011, Pages 1-24

  Finkbeiner, Steven ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHAPERONE; HD PROTEIN, HUMAN; NERVE PROTEIN; NUCLEAR PROTEIN; PEPTIDE; POLYGLUTAMINE; REPETITIVE DNA;

AGING; CELL INCLUSION; CHEMISTRY; GENETIC ASSOCIATION; GENETICS; HUMAN; HUNTINGTON CHOREA; METABOLISM; PATHOLOGY; PHYSIOLOGY; PROTEIN FOLDING; REVIEW;

AGING; DNA REPEAT EXPANSION; GENETIC ASSOCIATION STUDIES; HUMANS; HUNTINGTON DISEASE; INCLUSION BODIES; MOLECULAR CHAPERONES; NERVE TISSUE PROTEINS; NUCLEAR PROTEINS; PEPTIDES; PROTEIN FOLDING;

EID: 80054792814     PISSN: None     EISSN: 19430264     Source Type: Journal    
DOI: 10.1101/cshperspect.a007476     Document Type: Article

References (206)

1. Al-Ramahi I, Lam YC, Chen H-K, de Gouyon B, Zhang M, Pérez AM, Branco J, de Haro M, Patterson C, Zoghbi HY, et al. 2006. CHIP protects from the neurotoxicity of expanded and wild-type ataxin-1 and promotes their ubiquitination and degradation. J Biol Chem 281: 26714-26724.
2. Ardley HC, Hung C-C, Robinson PA. 2005. The aggravating role of the ubiquitin-proteasome system in neurodegeneration. FEBS Lett 579: 571-576.
3. Arrasate M, Finkbeiner S. 2005. Automated microscope system for determining factors that predict neuronal fate. Proc Natl Acad Sci 102: 3840-3845.
4. Arrasate M, Mitra S, Schweitzer ES, Segal MR, Finkbeiner S. 2004. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431: 805-810.
5. Augood SJ, Faull RLM, Love DR, Emson PC. 1996. 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 72: 1023-1036.
6. Babu JR, Geetha T, WootenMW. 2005. Sequestosome 1/p62 shuttles polyubiquitinated tau for proteasomal degradation. J Neurochem 94: 192-203.
7. Bates GP. 2005. History of genetic disease: The molecular genetics ofHuntington disease-a history. Nat Rev Genet 6: 766-773.
8. Beal MF. 1995. Aging, energy, and oxidative stress in neurodegenerative diseases. Ann Neurol 38: 357-366.
9. Becher MW, Kotzuk JA, Sharp AH, Davies SW, Bates GP, Price DL, Ross CA. 1998. Intranuclear neuronal inclusions inHuntington's disease and Dentatorubral and Pallidoluysian atrophy-Correlation between the density of inclusions and IT-15 CAG triplet repeat length. Neurobiol Dis 4: 387-397.
10. Behrends C, Langer CA, Boteva R, Böttcher UM, Stemp MJ, Schaffar G, Rao BV, Giese A, Kretzschmar H, Siegers K, et al. 2006. Chaperonin TRiC promotes the assembly of polyQ expansion proteins into nontoxic oligomers. Mol Cell 23: 887-897.
11. Bence NF, Sampat RM, Kopito RR. 2001. Impairment of the ubiquitin-proteasome system by protein aggregation. Science 292: 1552-1555.
12. Bennett EJ, Bence NF, Jayakumar R, Kopito RR. 2005. Global impairment of the ubiquitin-proteasome system by nuclear or cytoplasmic protein aggregates precedes inclusion body formation. Mol Cell 17: 351-365.
13. Bett JS, Goellner GM, Woodman B, Pratt G, Rechsteiner M, Bates GP. 2006. Proteasome impairment does not contribute to pathogenesis in R6/2 Huntington's disease mice: Exclusion of proteasome activator REGg as a therapeutic target. Hum Mol Genet 15: 33-44.
14. Bezard E, Gross CE, Brotchie JM. 2003. Presymptomatic compensation in Parkinson's disease is not dopaminemediated. Trends Neurosci 26: 215-221.
15. Bodner RA, Outeiro TF, Altmann S, Maxwell MM, Cho SH, Hyman BT, McLean PJ, Young AB, Housman DE, Kazantsev AG. 2006. Pharmacological promotion of inclusion formation: A therapeutic approach for Huntington's and Parkinson's disease. Proc Natl Acad Sci 103: 4246-4251.
16. Boudreau RL, McBride JL, Martins I, Shen S, Xing Y, Carter BJ, Davidson BL. 2009. Nonallele-specific silencing of mutant and wild-type huntingtin shows therapeutic efficacy in Huntington's disease mice. Mol Ther 17: 1053-1063.
17. Bowman AB, Lam YC, Jafar-Nejad P, Chen H-K, Richman R, Samaco RC, Fryer JD, Kahle JJ, Orr HT, Zoghbi HY. 2007. Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat Genet 39: 373-379.
18. Bowman AB, Yoo S-Y, Dantuma NP, Zoghbi HY. 2005. 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 Genet 14: 679-691.
19. Brandt J, Bylsma FW, Gross R, Stine OC, Ranen N, Ross CA. 1996. Trinucleotide repeat length and clinical progression in Huntington's disease. Neurology 46: 527-531.
20. Carmichael J, Chatellier J, Woolfson A, Milstein C, Fersht AR, Rubinsztein DC. 2000. Bacterial and yeast chaperones reduce both aggregate formation and cell death in mammalian cell models of Huntington's disease. Proc Natl Acad Sci 97: 9701-9705.
21. Chai Y, Koppenhafer SL, Shoesmith SJ, Perez MK, Paulson HL. 1999. Evidence for proteasome involvement in polyglutamine disease: Localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum Mol Genet 8: 673-682.
22. Chai Y, Shao J, Miller VM, Williams A, Paulson HL. 2002. Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis. Proc Natl Acad Sci 99: 9310-9315.
23. Charvin D, Vanhoutte P, Pages C, Borrelli E, Caboche J. 2005. Unraveling a role for dopamine in Huntington's disease: The dual role of reactive oxygen species and D2 receptor stimulation. Proc Natl Acad Sci 102: 12218-12223.
24. Chen S, Ferrone FA, Wetzel R. 2002b. Huntington's disease age-of-onset linked to polyglutamine aggregation nucleation. Proc Natl Acad Sci 99: 11884-11889.
25. Chen S, Berthelier V, Hamilton JB, O'Nuallain B, Wetzel R. 2002a. Amyloid-like features of polyglutamine aggregates and their assembly kinetics. Biochemistry 41: 7391-7399.
26. Ciechanover A, Brundin P. 2003. The ubiquitin proteasome system in neurodegenerative diseases: Sometimes the chicken, sometimes the egg. Neuron 40: 427-446.
27. Clarke G, Collins RA, Leavitt BR, Andrews DF, Hayden MR, Lumsden CJ, McInnes RR. 2000. A one-hit model of cell death in inherited neuronal degenerations. Nature 406: 195-199.
28. Cuervo AM, Bergamini E, Brunk UT, Dröge W, Ffrench M, Terman A. 2005. Autophagy and aging: The importance of maintaining "clean" cells. Autophagy 1: 131-140.
29. Cummings CJ, Sun Y, Opal P, Anatalffy B, Mestril R, Orr HT, Dillmann WH, Zoghbi HY. 2001. Over-expression of inducible HSP70 chaperone suppresses neuropathology and improves motor function in SCA1 mice. Hum Mol Genet 10: 1511-1518.
30. Davies SW, Beardsall K, Turmaine M, DiFiglia M, Aronin N, Bates GP. 1998. Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions? Lancet 351: 131-133.
31. Davies SW, Turmaine M, Cozens BA, DiFiglia M, Sharp AH, Ross CA, Scherzinger E, Wanker EE, Mangiarini L, Bates GP. 1997. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell 90: 537-548.
32. Díaz-Hernández M, Valera AG, Morán MA, Gómez-Ramos P, Alvarez-Castelao B, Castaño JG, Hernández F, Lucas JJ. 2006. Inhibition of 26S proteasome activity by huntingtin filaments but not inclusion bodies isolated from mouse and human brain. J Neurochem 98: 1585-1596.
33. DiFiglia M, Sapp E, Chase KO, Davies SW, Bates GP, Vonsattel JP, Aronin N. 1997. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277: 1990-1993.
34. DiFiglia M, Sena-Esteves M, Chase K, Sapp E, Pfister E, Sass M, Yoder J, Reeves P, Pandey RK, Rajeev KG, et al. 2007. Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits. ProcNatl Acad Sci 104: 17204-17209.
35. Ding Q, Keller JN. 2001. Proteasomes and proteasome inhibition in the central nervous system. Free Radic Biol Med 31: 574-584.
36. Ding Q, Lewis JJ, Strum KM, Dimayuga E, Bruce-Keller AJ, Dunn JC, Keller JN. 2002. Polyglutamine expansion, protein aggregation, proteasome activity, and neural survival. J Biol Chem 277: 13935-13942.
37. Donaldson KM, Li W, Ching KA, Batalov S, Tsai C-C, Joazeiro CAP. 2003. Ubiquitin-mediated sequestration of normal cellular proteins into polyglutamine aggregates. Proc Natl Acad Sci 100: 8892-8897.
38. Duvick L, Barnes J, Ebner B, Agrawal S, Andresen M, Lim J, Giesler G, Zoghbi H, Orr HT. 2010. SCA1-like disease in mice expressing wild type ataxin-1 with a serine to aspartic acid replacement at residue 776. Neuron 67: 929-935.
39. Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M. 1993. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nat Genet 4: 387-392.
40. Faber PW, Alter JR, MacDonald ME, Hart AC. 1999. Polyglutamine-mediated dysfunction and apoptotic death of a Caenorhabditis elegans sensory neuron. Proc Natl Acad Sci 96: 179-184.
41. Finkbeiner S, Cuervo AM, Morimoto RI, Muchowski PJ. 2006. Disease-modifying pathways in neurodegeneration. J Neurosci 26: 10349-10357.
42. Floyd JA, Hamilton BA. 1999. Intranuclear inclusions and the ubiquitin-proteasome pathway: Digestion of a red herring? Neuron 24: 765-766.
43. Fortun J, DunnWA Jr, Joy S, Li J, Notterpek L. 2003. Emerging role for autophagy in the removal of aggresomes in Schwann cells. J Neurosci 23: 10672-10680.
44. Fowler DM, Koulov AV, Alory-Jost C, Marks MS, Balch WE, Kelly JW. 2006. Functional amyloid formation within mammalian tissue. PLoS Biol 4: e6 (0100-0107).
45. Gaczynska M, Osmulski PA, Ward WF. 2001. Caretaker or undertaker? The role of the proteasome in aging. Mech Aging Dev 122: 235-254.
46. Georgalis Y, Starikov EB, Hollenbach B, Lurz R, Scherzinger E, Saenger W, Lehrach H, Wanker EE. 1998. Huntingtin aggregation monitored by dynamic light scattering. Proc Natl Acad Sci 95: 6118-6121.
47. Gething M-J. 1996. Molecular chaperones: Clasping the prize. Curr Biol 6: 1573-1576.
48. Gidalevitz T, Ben-Zvi A, Ho KH, Brignull HR, Morimoto RI. 2006. Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311: 1471-1474.
49. Ginovart N, Lundin A, Farde L, Halldin C, Backman L, Swahn CG, Pauli S, Sedvall G. 1997. PET study of the pre-and post-synaptic dopaminergic markers for the neurodegenerative process inHuntington's disease. Brain 120: 503-514.
50. Glabe CG, Kayed R. 2005. Common structure and toxic function of amyloid oligomers implies a common mechanism of pathogenesis. Neurology, S74-S78.
51. Glover JR, Lindquist S. 1998. Hsp104, Hsp70, and Hsp40: A novel chaperone system that rescues previously aggregated proteins. Cell 94: 73-82.
52. Goellner GM, Rechsteiner M. 2003. Are Huntington's and polyglutamine-based ataxias proteasome storage diseases? Int J Biochem Cell Biol 35: 562-571.
53. Goldberg YP, Kalchman MA, Metzler M, Nasir J, Zeisler J, Graham R, Koide HB, O'Kusky J, Sharp AH, Ross CA, et al. 1996. Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. Hum Mol Genet 5: 177-185.
54. Gray M, Shirasaki DI, Cepeda C, André VM, Wilburn B, Lu X-H, Tao J, Yamazaki I, Li S-H, Sun YE, et al. 2008. Fulllength human mutant huntingtin with a stable polyglutamine repeat can elicit progressive and selective neuropathogenesis in BACHD mice. J Neurosci 28: 6182-6195.
55. Graybiel AM. 2004. Network-level neuroplasticity in cortico-basal ganglia pathways. Parkinsonism Relat Disord 10: 293-296.
56. Group THsDCR. 1993. A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. Cell 72: 971-983.
57. Gusella JF, MacDonald ME. 2006. Huntington's disease: Seeing the pathogenic process through a genetic lens. Trends Biochem Sci 31: 533-540.
58. Gutekunst C-A, Li S-H, Yi H, Mulroy JS, Kuemmerle S, Jones R, Rye D, Ferrante RJ, Hersch SM, Li X-J. 1999. Nuclear and neuropil aggregates in Huntington's disease: Relationship to neuropathology. J Neurosci 19: 2522-2534.
59. Harper P. 2002. Huntington's disease: A historical background. In Huntington's Disease, (ed. G. Bates, P.S. Harper, L. Jones), pp. 3-37. Oxford, Oxford University Press.
60. Harper SQ, Staber PD, He X, Eliason SL, Martins IH, Mao Q, Yang L, Kotin RM, Paulson HL, Davidson BL. 2005. RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model. Proc Natl Acad Sci 102: 5820-5825.
61. Heydari AR, Takahashi R, Gutsmann A, You S, Richardson A. 1994. Hsp70 and aging. Experientia 50: 1092-1098.
62. Hollenbach B, Scherzinger E, Schweiger K, Lurz R, Lehrach H, Wanker EE. 1999. Aggregation of truncated GST-HD exon 1 fusion proteins containing normal range and expanded glutamine repeats. Philos Trans R Soc Lond B Biol Sci 354: 991-994.
63. Holmberg CI, Staniszewski KE, Mensah KN, Matouschek A, Morimoto RI. 2004. Inefficient degradation of truncated polyglutamine proteins by the proteasome. EMBO J 23: 4307-4318.
64. Huang CC, Faber PW, Persichetti F, Mittal V, Vonsattel J-P, MacDonald ME, Gusella JF. 1998. Amyloid formation by mutant huntingtin: Threshold, progressivity and recruitment of normal polyglutamine proteins. Somat Cell Mol Genet 24: 217-233.
65. Humbert S, Bryson EA, Cordelières FP, Connors NC, Datta SR, Finkbeiner S, Greenberg ME, Saudou F. 2002. The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves huntingtin phosphorylation by Akt. Dev Cell 3: 1-20.
66. Huntington G. 1872. On chorea. In The Medical and Surgical Reporter: A Weekly Journal, (ed. SW. Butler), pp. 317-321. Philadelphia.
67. Ignatova Z, Gierasch LM. 2006. Extended polyglutamine tracts cause aggregation and structural perturbation of an adjacent β barrel protein. J Biol Chem 281: 12959-12967.
68. Iwata A, Riley BE, Johnston JA, Kopito RR. 2005. HDAC6 and microtubules are required for autophagic degradation of aggregated huntingtin. J Biol Chem 280: 40282-40292.
69. Jackson GR, Salecker I, Dong X, Yao X, Arnheim N, Faber PW, MacDonald ME, Zipursky SL. 1998. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron 21: 633-642.
70. Jana NR, Nukina N. 2003. Recent advances in understanding the pathogenesis of polyglutamine diseases: Involvement of molecular chaperones and ubiquitinproteasome pathway. J Chem Neuroanat 26: 95-101.
71. Jana NR, Tanaka M, Wang G-H, Nukina N. 2000. Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: Their role in suppression of aggregation and cellular toxicity. Hum Mol Genet 9: 2009-2018.
72. Johnston JA, Ward CL, Kopito RR. 1998. Aggresomes: A cellular response to misfolded proteins. J Cell Biol 143: 1883-1898.
73. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao T-P. 2003. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 115: 727-738.
74. Kayed R, Head E, Thompson JL, McIntire TM, Milton SC, Cotman CW, Glabe CG. 2003. Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis. Science 300: 486-489.
75. Kayed R, Sokolov Y, Edmonds B, McIntire TM, Milton SC, Hall JE, Glabe CG. 2004. Permeabilization of lipid bilayers is a common conformation-dependent activity of soluble amyloid oligomers in protein misfolding diseases. J Biol Chem 279: 46363-46366.
76. Kazantsev A, Preisinger E, Dranovsky A, Goldgaber D, Housman D. 1999. Insoluble detergent-resistant aggregates form between pathological and nonpathological lengths of polyglutamine in mammalian cells. Proc Natl Acad Sci 96: 11404-11409.
77. Kazemi-Esfarjani P, Benzer S. 2000. Genetic suppression of polyglutamine toxicity in Drosophila. Science 287: 1837-1840.
78. Kegel KB, Kim M, Sapp E, McIntyre C, Castaño JG, Aronin N, DiFiglia M. 2000. Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy. J Neurosci 20: 7268-7278.
79. Keller JN, Dimayuga E, Chen Q, Thorpe J, Gee J, Ding Q. 2004. Autophagy, proteasomes, lipofuscin, and oxidative stress in the aging brain. Int J Biochem Cell Biol 36: 2376-2391.
80. Kim J, Klionsky DJ. 2000. Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu Rev Biochem 69: 303-342.
81. KimMW, Chelliah Y, KimSW, Otwinowski Z, Bezprozvanny I. 2009. Secondary structure of Huntingtin aminoterminal region. Structure 17: 1205-1212.
82. Kim S, Nollen EAA, Kitagawa K, Bindokas VP, Morimoto RI. 2002. Polyglutamine protein aggregates are dynamic. Nat Cell Biol 4: 826-831.
83. Kim S, Nollen EAA, Kitagawa K, Bindokas VP, Morimoto RI. 2003. Polyglutamine protein aggregates are dynamic. Nat Cell Biol 4: 826-831.
84. Kitamura A, Kubota H, Pack C-G, Matsumoto G, Hirayama S, Takahashi Y, Kimura H, Kinjo M, Morimoto RI, Nagata K. 2006. Cytosolic chaperonin prevents polyglutamine toxicity with altering the aggregation state. Nat Cell Biol 8: 1163-1170.
85. Klein FAC, Pastore A, Masino L, Zeder-Lutz G, Nierengarten H, Oulad-Abdelghani M, Altschuh D, Mandel J-L, Trottier Y. 2007. Pathogenic and non-pathogenic polyglutamine tracts have similar structural properties: Towards a length-dependent toxicity gradient. J Mol Biol 371: 235-244.
86. Klement IA, Skinner PJ, KaytorMD, Yi H, Hersch SM, Clark HB, Zoghbi HY, Orr HT. 1998. Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic mice. Cell 95: 41-53.
87. Klivenyi P, Vecsei L. 1997. Neurodegeneration: Aging and dementia. Etiopathogenic role of electron transport disorders. Therapeutic possibilities. Orv Hetil 138: 331-335.
88. Kobayashi Y, Kume A, Li M, Doyu M, Hata M, Ohtsuka K, Sobue G. 2000. Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cells expressing truncated androgen receptor protein with expanded polyglutamine tract. J Biol Chem 275: 8772-8778.
89. Kratter IH, Finkbeiner S. 2010. PolyQ disease:Too many Q's, too much function? Neuron 67: 897-899.
90. Krobitsch S, Lindquist S. 2000. Aggregation of huntingtin in yeast varies with the length of the polyglutamine expansion and the expression of chaperone proteins. Proc Natl Acad Sci 97: 1589-1594.
91. Kuemmerle S, Gutekunst C-A, Klein AM, Li X-J, Li S-H, Beal F, Hersch SM, Ferante RJ. 1999. Huntingtin aggregates may not predict neuronal death in Huntington's disease. Ann Neurol 46: 842-849.
92. Kuhn A, Goldstein DR, Hodges A, Strand AD, Sengstag T, Kooperberg C, Becanovic K, Pouladi MA, Sathasivam K, Cha J-HJ, et al. 2007. 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 16: 1845-1861.
93. Lam YC, Bowman AB, Jafar-Nejad P, Lim J, Richman R, Fryer JD, Hyun ED, Duvick LA, Orr HT, Botas J, et al. 2006. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell 127: 1335-1347.
94. Le Moine C, Normand E, Guitteny AF, Fouque B, Teoule R, Bloch B. 1990. Dopamine receptor gene expression by enkephalin neurons in rat forebrain. Proc Natl Acad Sci 87: 230-234.
95. Lelouard H, Ferrand V, Marguet D, Bania J, Camosseto V, David A, Gatti E, Pierre P. 2004. Dendritic cell aggresome-like induced structures are dedicated areas for ubiquitination and storage of newly synthesized defective proteins. J Cell Biol 164: 667-675.
96. Li LB, Yu Z, Teng X, Bonini NM. 2008. RNA toxicity is a component of ataxin-3 degeneration in Drosophila. Nature 453: 1107-1111.
97. Lim J, Crespo-Barreto J, Jafar-Nejad P, Bowman AB, Richman R, Hill DE, Orr HT, Zoghbi HY. 2008. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature 452: 713-718.
98. Lüders J, Demand J, Höhfeld J. 2000. The ubiquitin-related BAG-1 provides a link between the molecular chaperones Hsc70/Hsp70 and the proteasome. J Biol Chem 275: 4613-4617.
99. Lund JC. 1860. Chorea Sti Viti I Stersdalen. In Uddrag af Distriktsoege J C Lunds Medicinalberetning for 1860, pp. 137-138. (Beretning om Sundhedstilstandenm, Norway).
100. MacDonald ME, Barnes G, Srinidhi J, Duyao MP, Ambrose CM, Myers RH, Gray J, Conneally PM, Young A, Penney J. 1993. Gametic but not somatic instability of CAG repeat length inHuntington's disease. J Med Genet 30: 982-986.
101. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier Y, Lehrach H, Davies SW, et al. 1996. Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87: 493-506.
102. Marshall PE, Landis DM, Zalneraitis EL. 1983. Immunocytochemical studies of substance Pand leucine-enkephalin in Huntington's disease. Brain Res 289: 11-26.
103. Masino L, Kelly G, Leonard K, Trottier Y, Pastore A. 2002. Solution structure of polyglutamine tracts in GSTpolyglutamine fusion proteins. FEBS Lett 513: 267-272.
104. Massey AC, Zhang C, Cuervo AM. 2006. Chaperonemediated autophagy in aging and disease. Curr Top Dev Biol 73: 205-235.
105. McCampbell A, Taylor JP, Taye AA, Robitschek J, Li M, Walcott J, Merry D, Chai Y, Paulson H, Sobue G, et al. 2000. CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet 9: 2197-2202.
106. Meijer AJ, Codogno P. 2004. Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36: 2445-2462.
107. Menalled L, El-Khodor BF, Patry M, Suárez-Fariñas M, Orenstein SJ, Zahasky B, Leahy C, Wheeler V, Yang XW, MacDonald M, et al. 2009. Systematic behavioral evaluation of Huntington's disease transgenic and knock-in mouse models. Neurobiol Dis 35: 319-336.
108. Michalik A, Van Broeckhoven C. 2004. Proteasome degrades soluble expanded polyglutamine completely and efficiently. Neurobiol Dis 16: 202-211.
109. Miller J, Arrasate M, Shaby BA, Mitra S, Masliah E, Finkbeiner S. 2010a. Quanitative relationships between huntingtin levels, polyglutamine length, inclusion body formation, and neuronal death provide novel insight into Huntington's disease molecular pathogenesis. J Neurosci 30: 10541-10550.
110. Miller VM, Nelson RF, Gouvion CM, Williams A, Rodriguez-Lebron E, Harper SQ, Davidson BL, Rebagliati MR, Paulson HL. 2005. CHIP suppresses polyglutamine aggregation and toxicity in vitro and in vivo. J Neurosci 25: 9152-9161.
111. Mitra S, Finkbeiner S. 2008. The ubiquitin-proteasome pathway in Huntington's disease. The Scientific World Journal 8: 421-433.
112. Mitra S, Tsvetkov AS, Finkbeiner S. 2009. Single neuron ubiquitin-proteasome dynamics accompanying inclusion body formation in Huntington's disease. J Biol Chem 284: 4398-4403.
113. Muchowski PJ, Wacker JL. 2005. Modulation of neurodegeneration by molecular chaperones. Nat Rev Neurosci 6: 11-22.
114. Muchowski PJ, Ning K, D'Souza-Schorey C, Fields S. 2002. Requirement of an intact microtubule cytoskeleton for aggregation and inclusion body formation by a mutant huntingtin fragment. Proc Natl Acad Sci 99: 727-732.
115. Muchowski PJ, Schaffar G, Sittler A, Wanker EE, Hayer-Hartl MK, Hartl FU. 2000. Hsp70 and Hsp40 chaperones can inhibit self-assembly of polyglutamine proteins into amyloid-like fibrils. Proc Natl Acad Sci 97: 7841-7846.
116. Myers RH, Vonsattel JP, Stevens TJ, Cupples LA, Richardson EP, Martin JB, Bird ED. 1988. Clinical and neuropathologic assessment of severity inHuntington's disease. Neurology 38: 341-347.
117. Myung J, Kim KB, Crews CM. 2001. The ubiquitinproteasome pathway and proteasome inhibitors. Med Res Rev 21: 245-273.
118. Nagai Y, Fujikake N, Ohno K, Higashiyama H, Popiel HA, Rahadian J, Yamaguchi M, Strittmatter WJ, Burke JR, Toda T. 2003. Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila. Hum Mol Genet 12: 1253-1259.
119. Nagai Y, Inui T, Popiel HA, Fujikake N, Hasegawa K, Urade Y, Goto Y, Naiki H, Toda T. 2007. A toxic monomeric conformer of the polyglutamine protein. Nat Struct Mol Biol 14: 332-340.
120. Nagaoka U, Kim K, Jana NR, Doi H, Maruyama M, Mitsui K, Oyama F, Nukina N. 2004. Increased expression of p62 in expanded polyglutamine-expressing cells and its association with polyglutamine inclusions. J Neurochem 91: 57-68.
121. Nance MA, Myers RH. 2001. Juvenile onset Huntington's disease-Clinical and research perspectives. Ment Retard Dev Disabil Res Rev 7: 153-157.
122. Nandi PK. 1996. Protein conformation and disease. Vet Res 27: 373-382.
123. Nedelsky NB, Pennuto M, Smith RB, Palazzolo I, Moore J, Nie Z, Neale G, Taylor JP. 2010. Native functions of the androgen receptor are essential to pathogenesis in a Drosophila model of spinobulbar muscular atrophy. Neuron 67: 936-952.
124. Nollen EAA, Garcia SM, van Haaften G, Kim S, Chavez A, Morimoto RI, Plasterk RHA. 2004. Genome-wide RNA interference screen identifies previously undescribed regulators of polyglutamine aggregation. Proc Natl Acad Sci 101: 6403-6408.
125. Okamoto S, Pouladi MA, Talantova M, Yao D, Xia P, Ehrnhoefer DE, Zaidi R, Clemente A, Kaul M, Graham RK, et al. 2009. Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin. Nat Med 15: 1407-1413.
126. Onodera O, Burke JR, Miller SE, Hester S, Tsuji S, Roses AD, Strittmatter WJ. 1997. Oligomerization of expanded-polyglutamine domain fluorescent fusion proteins in cultured mammalian cells. Biochem Biophys Res Commun 238: 599-605.
127. Orr HT. 2004. Neuron protection agency. Nature 431: 747-748.
128. Ortega Z, Díaz-Hernández M, Maynard CJ, Hernández F, Dantuma NP, Lucas JJ. 2010. Acute polyglutamine expression in inducible mouse model unravels ubiquitin/proteasome system impairment and permanent recovery attributable to aggregate formation. J Neurosci 30: 3675-3688.
129. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, HoKO, Yu G-Q, Kreitzer A, et al. 2007. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 55: 697-711.
130. Pandey UB, Nie Z, Batlevi Y, McCray BA, Ritson GP, Nedelsky NB, Schwartz SL, DiProspero NA, Knight MA, Schuldiner O, et al. 2007. HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS. Nature 447: 859-863.
131. ParsellDA, Kowal AS, Singer MA, Lindquist S. 1994. Protein disaggregation mediated by heat-shock protein Hsp104. Nature 372: 475-478.
132. Paulsen JS, Langbehn DR, Stout JC, Aylward E, Ross CA, Nance M, Guttman M, Johnson S, MacDonald M, Beglinger LJ, et al. 2008. Detection of Huntington's disease decades before diagnosis: The Predict-HD study. J Neurol Neurosurg Psychiatry 79: 874-880.
133. Penney JB Jr, Vonsattel JP, MacDonald ME, Gusella JF, Myers RH. 1997. CAG repeat number governs the development rate of pathology inHuntington's disease. Ann Neurol 41: 689-692.
134. Persichetti F, Carlee L, Faber PW, McNeil SM, Ambrose CM, Srinidhi J, Anderson M, Barnes GJ, Gusella JF, MacDonald ME. 1996. Differential expression of normal and mutant Huntington's disease gene alleles. Neurobiol Dis 3: 183-190.
135. Petersén A, Larsen KE, Behr GG, Romero N, Przedborski S, Brundin P, SulzerD. 2001. ExpandedCAGrepeats in exon 1 of the Huntington's disease gene stimulate dopaminemediated striatal neuron autophagy and degeneration. Hum Mol Genet 10: 1243-1254.
136. Petrucelli L, Dawson TM. 2004. Mechanism of neurodegenerative disease: Role of the ubiquitin proteasome system. Ann Med 36: 315-320.
137. Picconi B, Pisani A, Barone I, Bonsi P, Centonze D, Bernardi G, Calabresi P. 2005. Pathological synaptic plasticity in the striatum: Implications for Parkinson's disease. Neurotoxicology 26: 779-783.
138. Poirier MA, Jiang H, Ross CA. 2005. A structure-based analysis of huntingtin mutant polyglutamine aggregation and toxicity: Evidence for a compact β-sheet structure. Hum Mol Genet 14: 765-774.
139. Preisinger E, Jordan BM, Kazantsev A, Housman D. 1999. Evidence for a recruitment and sequestration mechanism inHuntington's disease. Philos Trans R Soc Lond B Biol Sci 354: 1029-1034.
140. Qin Z-H, Wang Y, Kegel KB, Kazantsev A, Apostol BL, Thompson LM, Yoder J, Aronin N, DiFiglia M. 2003. Autophagy regulates the processing of amino terminal huntingtin fragments. Hum Mol Genet 12: 3231-3244.
141. n repeats in parent-offspring pairs with Huntington disease. Am J Hum Genet 57: 593-602.
142. Ravikumar B, Rubinsztein DC. 2004. Can autophagy protect against neurodegeneration caused by aggregateprone proteins? Neuroreport 15: 2443-2445.
143. Ravikumar B, Duden R, Rubinsztein DC. 2002. Aggregateprone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 11: 1107-1117.
144. Richfield EK, Maguire-Zeiss KA, Vonkeman HE, Voorn P. 1995. Preferential loss of preproenkephalin versus preprotachykinin neurons from the striatum of Huntington's disease patients. Ann Neurol 38: 852-861.
145. Rideout HJ, Lang-Rollin I, Stefanis L. 2004. Involvement of macroautophagy in the dissolution of neuronal inclusions. Int J Biochem Cell Biol 36: 2551-2562.
146. Rogers D, Leavitt B. 2004. HD aggregates accelerate autophagy. Clin Genet 66: 293-294.
147. Rosas HD, Hevelone ND, Zaleta AK, Greve DN, Salat DH, Fischl B. 2005. Regional cortical thinning in preclinical Huntington disease and its relationship to cognition. Neurology 65: 745-747.
148. Ross CA. 1997. Intranuclear neuronal inclusions: A common pathogenic mechanism for glutamine-repeat neurodegenerative diseases. Neuron 19: 1147-1150.
149. Rubinsztein DC, Wyttenbach A, Rankin J. 1999. Intracellular inclusions, pathological markers in disease caused by expanded polyglutamine tracts? J Med Genet 36: 265-270.
150. Rubinsztein DC, Leggo J, Coles R, Almqvist E, Biancalana V, Cassiman J-J, Chotai K, Connarty M, Craufurd D, Curtis A, et al. 1996. Phenotypic characterization of individuals with 30-40 CAG repeats in theHuntington disease (HD) gene reveals HD cases with 36 repeats and apparently normal elderly individuals with 36-39 repeats. Am J Hum Genet 59: 16-22.
151. Sánchez I, Mahlke C, Yuan J. 2003. Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders. Nature 421: 373-379.
152. Sapp E, Ge P, Aizawa H, Bird E, Penney J, Young AB, Vonsattel J-P, DiFiglia M. 1995. Evidence for a preferential loss of enkephalin immunoreactivity in the external globus pallidus in low grade Huntington's disease using high resolution image analysis. Neuroscience 64: 397-404.
153. Saric T, Graef CI, Goldberg AL. 2004. Pathway for degradation of peptides generated by proteasomes: A key role for thimet oligopeptidase and other metallopeptidases. J Biol Chem 279: 46723-46732.
154. Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC. 2007a. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and α-synuclein. J Biol Chem 282: 5641-5652.
155. Sarkar S, Perlstein EO, Imarisio S, Pineau S, Cordenier A, Maglathlin RL, Webster JA, Lewis TA, O'Kane CJ, Schreiber SL, et al. 2007b. Small molecules enhance autophagy and reduce toxicity in Huntington's disease models. Nat Chem Biol 3: 331-338.
156. Sathasivam K, Lane A, Legleiter J, Warley A, Woodman B, Finkbeiner S, Paganetti P, Muchowski PJ, Wilson S, Bates GP. 2010. Identical oligomeric and fibrillar structures captured from the brains of R6/2 and knock-in mouse models of Huntington's disease. Hum Mol Genet 19: 65-78.
157. Satyal S, Schmidt E, Kitagawa K, Sondheimer N, Lindquist S, Kramer JM, Morimoto RI. 2000. Polyglutamine aggregates alter protein folding homeostasis in Caenorrhabditis elegans. Proc Natl Acad Sci 97: 5750-5755.
158. Saudou F, Finkbeiner S, Devys D, Greenberg ME. 1998. Huntingtin acts in the nucleus to induce apoptosis, but death does not correlate with the formation of intranuclear inclusions. Cell 95: 55-66.
159. Sax DS, Powsner R, Kim A, Tilak S, Bhatia R, Cupples LA, Myers RH. 1996. Evidence of cortical metabolic dysfunction in early Huntington's disease by single-photon-emission computed tomography. Mov Disord 11: 671-677.
160. Schaffer G, Breuer P, Boteva R, Behrends C, Tzetkov K, Stripple N, Hayer-Hartl M, Hartl F-U. 2004. Cellular toxicity of polyglutamine expansion proteins: Mechanism of transcription factor deactivation. Mol Cell 15: 95-105.
161. Scherzinger E, Lurz R, Turmaine M, Mangiarini L, Hollenbach B, Hasenbank R, Bates GP, Davies SW, Lehrach H, Wanker EE. 1997. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell 90: 549-558.
162. Scherzinger E, Sittler A, Schweiger K, Heiser V, Lurz R, Hasenbank R, Bates GP, Lehrach H, Wanker EE. 1999. Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: Implications for Huntington's disease pathology. Proc Natl Acad Sci 96: 4604-4609.
163. Shacka JJ, Roth KA, Zhang J. 2008. The autophagylysosomal degradation pathway: Role in neurodegenerative disease and therapy. Front Biosci 13: 718-736.
164. Shimohata T, Sato A, Burke JR, Strittmatter WJ, Tsuji S, Onodera O. 2002. Expanded polyglutamine stretches form an 'aggresome'. Neurosci Lett 323: 215-218.
165. Sieradzan KA, Mechan AO, Jones L, Wankers EE, Nukina N, Mann DMA. 1999. Huntington's disease intranuclear inclusions contain truncated, ubiquitinated huntingtin protein. Exp Neurol 156: 92-99.
166. Sisodia SS. 1998. Nuclear inclusions in glutamine repeat disorders: Are they pernicious, coincidental or beneficial? Cell 95: 1-4.
167. Slow EJ, Graham RK, Osmand AP, Devon RS, Lu G, Deng Y, Pearson J, Vaid K, Bissada N, Wetzel R, et al. 2005. Absence of behavioral abnormalities and neurodegeneration in vivo despite widespread neuronal huntingtin inclusions. Proc Natl Acad Sci 102: 11402-11407.
168. Snell RG, MacMillan JC, Cheadle JP, Fenton I, Lazarou LP, Davies P, MacDonald ME, Gusella JF, Harper PS, Shaw DJ. 1993. Relationship between trinucleotide repeat expansion and phenotypic variation inHuntington's disease. Nat Genet 4: 393-397.
169. Squitieri F, Gellera C, Cannella M, Mariotti C, Cislaghi G, Rubinsztein DC, Almqvist EW, Turner D, Bachoud-Lévi A-C, Simpson SA, et al. 2003. Homozygosity for CAG mutation in Huntington disease is associated with a more severe clinical course. Brain 126: 946-955.
170. Stenoien DL, Cummings CJ, Adams HP, Mancini MG, Patel K, DeMartino GN, Marcelli M, Weigel NL, Mancini MA. 1999. Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone. Hum Mol Genet 8: 731-741.
171. Subramaniam S, Sixt KM, Barrow R, Snyder SH. 2009. Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity. Science 324: 1327-1330.
172. Takahashi T, Kikuchi S, Katada S, Nagai Y, Nishizawa M, Onodera O. 2008. Soluble polyglutamine oligomers formed prior to inclusion body formation are cytotoxic. Hum Mol Genet 17: 345-356.
173. Tam S, Geller R, Spiess C, Frydman J. 2006. The chaperonin TRiC controls polyglutamine aggregation and toxicity through subunit-specific interactions. Nat Cell Biol 8: 1155-1162.
174. Tanzi RE, Bertram L. 2005. Twenty years of the Alzheimer's disease amyloid hypothesis: A genetic perspective. Cell 120: 545-555.
175. Taylor JP, Tanaka F, Robitschek J, Sandoval CM, Taye A, Markovic-Plese S, Fischbeck KH. 2003. Aggresomes protect cells by enhancing the degradation of toxic polyglutamine-containing protein. Hum Mol Genet 12: 749-757.
176. Taylor RC, Dillin A. 2011. Aging as an event of proteostasis collapse. Cold Spring Harb Perspect Biol doi:10.1101/cshperspect.a004440.
177. Telenius H, Almqvist E, Kremer B, Spence N, Squitieri F, Nichol K, Grandell U, Starr E, Benjamin C, Castaldo I. 1995. Somatic mosaicism in sperm is associated with intergenerational (CAG)n changes in Huntington disease. Hum Mol Genet 4: 189-195.
178. Telenius H, Kremer B, Goldberg YP, Theilmann J, Andrew SE, Zeisler J, Adam S, Greenberg C, Ives EJ, Clarke LA. 1994. Somatic and gonadal mosaicism of theHuntington disease gene CAG repeat in brain and sperm. Nat Genet 6: 409-414.
179. Telenius H, Kremer HP, Theilmann J, Andrew SE, Almqvist E, Anvret M, Greenberg C, Greenberg J, Lucotte G, Squitieri F. 1993. Molecular analysis of juvenile Huntington disease: The major influence on (CAG)n repeat length is the sex of the affected parent. Hum Mol Genet 2: 1535-1540.
180. Thakur AK, Yang W, Wetzel R. 2004. Inhibition of polyglutamine aggregate cytotoxicity by a structure-based elongation inhibitor. FASEB J 18: 923-925.
181. Trommer BL, Shah C, Yun SH, Gamkrelidze G, Pasternak ES, Blaine Stine W, Manelli A, Sullivan P, Pasternak JF, LaDu MJ. 2005. ApoE isoform-specific effects on LTP: Blockade by oligomeric amyloid-b1-42. Neurobiol Dis 18: 75-82.
182. Vacher C, Garcia-Oroz L, Rubinsztein DC. 2005. Overexpression of yeast hsp104 reduces polyglutamine aggregation and prolongs survival of a transgenic mouse model of Huntington's disease. Hum Mol Genet 14: 3425-3433.
183. Venkatraman P, Wetzel R, Tanaka M, Nukina N, Goldberg AL. 2004. Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins. Mol Cell 14: 95-104.
184. Vonsattel JP, Myers RH, Stevens TJ, Ferrante RJ, Bird ED, Richardson EP Jr. 1985. Neuropathological classification of Huntington's disease. J Neuropathol Exp Neurol 44: 559-577.
185. Wacker JL, Huang SY, Steele AD, Aron R, Lotz GP, Nguyen Q, Giorgini F, Roberson ED, Lindquist S, Masliah E, et al. 2009. Loss of Hsp70 exacerbates pathogenesis but not levels of fibrillar aggregates in a mouse model of Huntington's disease. J Neurosci 29: 9104-9114.
186. Wacker JL, Zareie MH, Fong H, Sarikaya M, Muchowski PJ. 2004. Hsp70 and Hsp40 attenuate formation of spherical and annular polyglutamine oligomers by partitioning monomer. Nat Struct Mol Biol 11: 1215-1222.
187. Waelter S, Boeddrich A, Lurz R, Scherzinger E, Lueder G, Lehrach H, Wanker EE. 2001. Accumulation of mutant huntingtin fragments in aggresome-like inclusion bodies as a result of insufficient protein degradation. Mol Biol Cell 12: 1393-1407.
188. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, Rowan MJ, Selkoe DJ. 2002. Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416: 535-539.
189. Wang X, Vitalis A, Wyczalkowski MA, Pappu RV. 2006. Characterizing the conformational ensemble of monomeric polyglutamine. Proteins 63: 297-311.
190. Wanker EE, Scherzinger E, Heiser V, Sittler A, Eickhoff H, Lehrach H. 1999. Membrane filter assay for detection of amyloid-like polyglutamine-containing protein aggregates. Methods Enzymol 309: 375-386.
191. Warrick JM, Chan HYE, Gray-Board GL, Chai Y, Paulson HL, Bonini NM. 1999. Suppression of polyglutaminemediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat Genet 23: 425-428.
192. Webb JL, Ravikumar B, Rubinsztein DC. 2004. Microtubule disruption inhibits autophagosome-lysosome fusion: Implications for studying the roles of aggresomes in polyglutamine diseases. Int J Biochem Cell Biol 36: 2541-2550.
193. Wexler NS, Lorimer J, Porter J, Gomez F, Moskowitz C, Shackell E, Marder K, Penchaszadeh G, Roberts SA, Gayan J, et al. 2004. Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset. Proc Natl Acad Sci101: 3498-3503.
194. Willingham S, Outeiro TF, DeVit MJ, Lindquist SL, Muchowski PJ. 2003. Yeast genes that enhance the toxicity of a mutant huntingtin fragment or α-synuclein. Science 302: 1769-1772.
195. Wirths O, Multhaup G, Bayer TA. 2004. A modified β-amyloid hypothesis: Intraneuronal accumulation of the β-amyloid peptide-the first step of a fatal cascade. J Neurochem 91: 513-520.
196. Wong SLA, Chan WM, Chan HYE. 2008b. Sodium dodecyl sulfate-insoluble oligomers are involved in polyglutamine degeneration. FASEB J 22: 3348-3357.
197. Wong ESP, Tan JMM, Soong W-E, Hussein K, Nukina N, Dawson VL, Dawson TM, Cuervo AM, Lim K-L. 2008a. Autophagy-mediated clearance of aggresomes is not a universal phenomenon. Hum Mol Genet 17: 2570-2582.
198. Wyttenbach A, Carmichael J, Swartz J, Furlong RA, Narain Y, Rankin J, Rubinsztein DC. 2000. 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 97: 2898-2903.
199. Yamamoto A, Lucas JJ, Hen R. 2000. Reversal of neuropathology and motor dysfunction in a conditional model of Huntington's disease. Cell 101: 57-66.
200. Yamamoto A, Cremona ML, Rothman JE. 2006. Autophagymediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway. J Cell Biol 172: 719-731.
201. Yang W, Dunlap JR, Andrews RB, Wetzel R. 2002. Aggregated polyglutamine peptides delivered to nuclei are toxic to mammalian cells. Hum Mol Genet 11: 2905-2917.
202. Ying W. 1996. A new hypothesis of neurodegenerative diseases: The deleterious network hypothesis. Med Hypotheses 47: 307-313.
203. Yoo S-Y, Pennesi ME, Weeber EJ, Xu B, Atkinson R, Chen S, Armstrong DL, Wu SM, Sweatt JD, Zoghbi HY. 2003. SCA7 knockin mice model human SCA7 and reveal gradual accumulation of mutant ataxin-7 in neurons and abnormalities in short-term plasticity. Neuron 37: 383-401.
204. Yu Z-X, Li S-H, Nguyen H-P, Li X-J. 2002. Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice. Hum Mol Genet 11: 905-914.
205. Zatloukal K, Stumptner C, Fuchsbichler A, Heid H, Schnoelzer M, Kenner L, Kleinert R, Prinz M, Aguzzi A, Denk H. 2002. p62 is a common component of cytoplasmic inclusions in protein aggregation diseases. Am J Pathol 160: 255-263.
206. 2-terminal fragment complexes that are promoted by the agedependent decrease in proteasome activity. J Cell Biol 163: 109-118.