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References (50)
-
S. Kuemmerle, C. Gutekunst, A. Klein, Xiao-Jiang Li, Shihua Li, M. Beal, S. Hersch, R. Ferrante (1999)
Huntingtin aggregates may not predict neuronal death in Huntington's diseaseAnnals of Neurology, 46
-
J. Vonsattel, R. Myers, Thomas Stevens, R. Ferrante, E. Bird, E. Richardson (1985)
Neuropathological Classification of Huntington's DiseaseJournal of Neuropathology and Experimental Neurology, 44
-
D. Martindale, A. Hackam, A. Wieczorek, L. Ellerby, C. Wellington, K. McCutcheon, R. Singaraja, P. Kazemi-Esfarjani, R. Devon, Seung Kim, D. Bredesen, F. Tufaro, M. Hayden (1998)
Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregatesNature Genetics, 18
-
I. Kovtun, C. McMurray (2001)
Trinucleotide expansion in haploid germ cells by gap repairNature Genetics, 27
-
T. Cristofaro, A. Affaitati, A. Feliciello, E. Avvedimento, S. Varrone (2000)
Polyglutamine-mediated aggregation and cell death.Biochemical and biophysical research communications, 272 3
-
Cynthia McMurray, Lakshmi Devi, L. Calavetta, James Douglass (1989)
Regulated expression of the prodynorphin gene in the R2C Leydig tumor cell line.Endocrinology, 124 1
-
Y. Narain, A. Wyttenbach, J. Rankin, R. Furlong, D. Rubinsztein (1999)
A molecular investigation of true dominance in Huntington’s diseaseJournal of Medical Genetics, 36
-
I. Klement, P. Skinner, M. Kaytor, H. Yi, S. Hersch, H. Clark, H. Zoghbi, H. Orr (1998)
Ataxin-1 Nuclear Localization and Aggregation Role in Polyglutamine-Induced Disease in SCA1 Transgenic MiceCell, 95
-
Moon-Gone Kim, Hong Lee, G. Laforet, Charmian McIntyre, E. Martin, Patrick Chang, Tae-Wan Kim, Marie Williams, P. Reddy, D. Tagle, F. Boyce, L. Won, A. Heller, N. Aronin, M. Difiglia (1999)
Mutant Huntingtin Expression in Clonal Striatal Cells: Dissociation of Inclusion Formation and Neuronal Survival by Caspase InhibitionThe Journal of Neuroscience, 19
-
N. Aronin, K. Chase, C. Young, E. Sapp, Cordula Schwarz, N. Matta, R. Kornreich, Bernhard Lanwehrmeyer, E. Bird, M. Beal, J. Vonsattel, T. Smith, R. Carraway, F. Boyce, A. Young, J. Penney, M. Difiglia (1995)
CAG expansion affects the expression of mutant huntingtin in the Huntington's disease brainNeuron, 15
-
M. Difiglia, E. Sapp, K. Chase, S. Davies, G. Bates, J. Vonsattel, N. Aronin (1997)
Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain.Science, 277 5334
-
G. Goellner, D. Tester, S. Thibodeau, E. Almqvist, Y. Goldberg, M. Hayden, C. McMurray (1997)
Different mechanisms underlie DNA instability in Huntington disease and colorectal cancer.American journal of human genetics, 60 4
-
C. Huang, P. Faber, F. Persichetti, V. Mittal, J. Vonsattel, M. MacDonald, J. Gusella (1998)
Amyloid Formation by Mutant Huntingtin: Threshold, Progressivity and Recruitment of Normal Polyglutamine ProteinsSomatic Cell and Molecular Genetics, 24
-
M. Becher, J. Kotzuk, A. Sharp, S. Davies, G. Bates, D. Price, C. Ross (1998)
Intranuclear Neuronal Inclusions in Huntington's Disease and Dentatorubral and Pallidoluysian Atrophy: Correlation between the Density of Inclusions andIT15CAG Triplet Repeat LengthNeurobiology of Disease, 4
-
C. Gutekunst, Shihua Li, Hong Yi, James Mulroy, S. Kuemmerle, Randi Jones, David Rye, R. Ferrante, S. Hersch, Xiao-Jiang Li (1999)
Nuclear and Neuropil Aggregates in Huntington’s Disease: Relationship to NeuropathologyThe Journal of Neuroscience, 19
-
I. Sánchez, Chi-jie Xu, P. Juo, Akira Kakizaka, J. Blenis, Junying Yuan (1999)
Caspase-8 Is Required for Cell Death Induced by Expanded Polyglutamine RepeatsNeuron, 22
-
Y. Trottier, D. Devys, G. Imbert, F. Saudou, Isabelle An, Y. Lutz, C. Weber, Y. Agid, E. Hirsch, J. Mandel (1995)
Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated formNature Genetics, 10
-
Ai Yamamoto, J. Lucas, R. Hen (2000)
Reversal of Neuropathology and Motor Dysfunction in a Conditional Model of Huntington's DiseaseCell, 101
-
E. Scherzinger, A. Sittler, Katja Schweiger, V. Heiser, R. Lurz, R. Hasenbank, G. Bates, H. Lehrach, E. Wanker (1999)
Self-assembly of polyglutamine-containing huntingtin fragments into amyloid-like fibrils: implications for Huntington's disease pathology.Proceedings of the National Academy of Sciences of the United States of America, 96 8
-
VC Wheeler (2000)
Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in Hdh Q92 and Hdh Q111 knock-in miceHum. Mol. Genet., 9
-
N. Hazeki, Tadashi Tukamoto, Jun Goto, Ichiro Kanazawa (2000)
Formic acid dissolves aggregates of an N-terminal huntingtin fragment containing an expanded polyglutamine tract: applying to quantification of protein components of the aggregates.Biochemical and biophysical research communications, 277 2
-
C. Wellington, L. Ellerby, A. Hackam, R. Margolis, M. Trifiro, R. Singaraja, K. McCutcheon, G. Salvesen, S. Propp, M. Bromm, Kathleen Rowland, Taiqi Zhang, D. Rasper, Sophie Roy, N. Thornberry, L. Pinsky, A. Kakizuka, C. Ross, D. Nicholson, D. Bredesen, M. Hayden (1998)
Caspase Cleavage of Gene Products Associated with Triplet Expansion Disorders Generates Truncated Fragments Containing the Polyglutamine Tract*The Journal of Biological Chemistry, 273
-
J. Cooper, G. Schilling, M. Peters, W. Herring, A. Sharp, Z. Kaminsky, J. Masone, F. Khan, M. Delanoy, D. Borchelt, V. Dawson, T. Dawson, C. Ross (1998)
Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture.Human molecular genetics, 7 5
-
J. Steffan, A. Kazantsev, O. Spasic-Boskovic, Marilee Greenwald, Ya-zhen Zhu, H. Göhler, E. Wanker, G. Bates, D. Housman, L. Thompson (2000)
The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription.Proceedings of the National Academy of Sciences of the United States of America, 97 12
-
V. Wheeler, Jacqueline White, C. Gutekunst, V. Vrbanac, Meredith Weaver, Xiao-Jiang Li, Shihua Li, Hong Yi, J. Vonsattel, J. Gusella, S. Hersch, W. Auerbach, A. Joyner, M. MacDonald (2000)
Long glutamine tracts cause nuclear localization of a novel form of huntingtin in medium spiny striatal neurons in HdhQ92 and HdhQ111 knock-in mice.Human molecular genetics, 9 4
-
K. Sieradzan, A. Mechan, Lesley Jones, Erich Wanker, N. Nukina, D. Mann (1999)
Huntington's Disease Intranuclear Inclusions Contain Truncated, Ubiquitinated Huntingtin ProteinExperimental Neurology, 156
-
Y. Goldberg, D. Nicholson, D. Rasper, M. Kalchman, H. Koide, R. Graham, M. Bromm, P. Kazemi-Esfarjani, N. Thornberry, J. Vaillancourt, M. Hayden (1996)
Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tractNature Genetics, 13
-
F. Nucifora, M. Sasaki, M. Peters, H. Huang, J. Cooper, M. Yamada, H. Takahashi, S. Tsuji, J. Troncoso, V. Dawson, T. Dawson, C. Ross (2001)
Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular ToxicityScience, 291
-
C. Wellington, R. Singaraja, L. Ellerby, Jane Savill, S. Roy, B. Leavitt, E. Cattaneo, A. Hackam, A. Sharp, N. Thornberry, D. Nicholson, D. Bredesen, M. Hayden (2000)
Inhibiting Caspase Cleavage of Huntingtin Reduces Toxicity and Aggregate Formation in Neuronal and Nonneuronal Cells*The Journal of Biological Chemistry, 275
-
AS Hackam (1998)
The influence of huntingtin protein size on nuclear localization and toxicityJ. Cell Biol., 141
-
V. Ona, Mingwei Li, J. Vonsattel, L. Andrews, Sohail Khan, W. Chung, A. Frey, A. Menon, Xiao-Jiang Li, P. Stieg, Junying Yuan, J. Penney, A. Young, J. Cha, R. Friedlander (1999)
Inhibition of caspase-1 slows disease progression in a mouse model of Huntington's diseaseNature, 399
-
S. Davies, M. Turmaine, Barbara Cozens, M. Difiglia, A. Sharp, C. Ross, E. Scherzinger, E. Wanker, L. Mangiarini, G. Bates (1997)
Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD MutationCell, 90
-
JPG Vonsattel, M DiFiglia (1998)
Huntington diseaseJ. Neuropath. Exp. Neurol., 57
-
A. Hackam, R. Singaraja, T. Zhang, L. Gan, M. Hayden (1999)
In vitro evidence for both the nucleus and cytoplasm as subcellular sites of pathogenesis in Huntington's disease.Human molecular genetics, 8 1
-
A. Reiner, R. Albin, K. Anderson, C. D'amato, J. Penney, A. Young (1988)
Differential loss of striatal projection neurons in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America, 85 15
-
A. Hackam, R. Singaraja, C. Wellington, M. Metzler, K. McCutcheon, Taiqi Zhang, M. Kalchman, M. Hayden (1998)
The Influence of Huntingtin Protein Size on Nuclear Localization and Cellular ToxicityThe Journal of Cell Biology, 141
-
J. Hedreen, C. Peyser, S. Folstein, C. Ross (1991)
Neuronal loss in layers V and VI of cerebral cortex in Huntington's diseaseNeuroscience Letters, 133
-
Gabriele Schilling, M. Becher, A. Sharp, H. Jinnah, Kui Duan, J. Kotzuk, H. Slunt, T. Ratovitski, J. Cooper, N. Jenkins, N. Copeland, D. Price, C. Ross, D. Borchelt (1999)
Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin.Human molecular genetics, 8 3
-
S. Sisodia (1998)
Nuclear Inclusions in Glutamine Repeat Disorders Are They Pernicious, Coincidental, or Beneficial?Cell, 95
-
Y. Trottier, Y. Lutz, G. Stevanin, G. Imbert, D. Devys, G. Cancel, F. Saudou, C. Weber, Gilles David, L. Tora, Y. Agid, A. Brice, J. Mandel (1995)
Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxiasNature, 378
-
He Li, Shihua Li, H. Johnston, P. Shelbourne, Xiao-Jiang Li (2000)
Amino-terminal fragments of mutant huntingtin show selective accumulation in striatal neurons and synaptic toxicityNature Genetics, 25
-
C. Ross (1997)
Intranuclear Neuronal Inclusions: A Common Pathogenic Mechanism for Glutamine-Repeat Neurodegenerative Diseases?Neuron, 19
-
A. Lunkes, J. Mandel (1998)
A cellular model that recapitulates major pathogenic steps of Huntington's disease.Human molecular genetics, 7 9
-
L. Mende-Mueller, T. Toneff, Shin‐Rong Hwang, M. Chesselet, V. Hook (2001)
Tissue-Specific Proteolysis of Huntingtin (htt) in Human Brain: Evidence of Enhanced Levels of N- and C-Terminal htt Fragments in Huntington's Disease StriatumThe Journal of Neuroscience, 21
-
I. Dragatsis, M. Levine, S. Zeitlin (2000)
Inactivation of Hdh in the brain and testis results in progressive neurodegeneration and sterility in miceNature Genetics, 26
-
E. Scherzinger, R. Lurz, M. Turmaine, L. Mangiarini, B. Hollenbach, R. Hasenbank, G. Bates, S. Davies, H. Lehrach, E. Wanker (1997)
Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In VivoCell, 90
-
F. Saudou, S. Finkbeiner, D. Devys, M. Greenberg (1998)
Huntingtin Acts in the Nucleus to Induce Apoptosis but Death Does Not Correlate with the Formation of Intranuclear InclusionsCell, 95
-
Shihua Li, Xiao-Jiang Li (1998)
Aggregation of N-terminal huntingtin is dependent on the length of its glutamine repeats.Human molecular genetics, 7 5
-
L. Mangiarini, K. Sathasivam, M. Seller, Barbara Cozens, Alex Harper, C. Hetherington, Martin Lawton, Y. Trottier, H. Lehrach, S. Davies, G. Bates (1996)
Exon 1 of the HD Gene with an Expanded CAG Repeat Is Sufficient to Cause a Progressive Neurological Phenotype in Transgenic MiceCell, 87
-
A. Sharp, S. Loev, Gabriele Schilling, Shihua Li, Xiao-Jiang Li, J. Bao, M. Wagster, J. Kotzuk, J. Steiner, A. Lo, J. Hedreen, S. Sisodia, S. Snyder, T. Dawson, D. Ryugo, C. Ross (1995)
Widespread expression of Huntington's disease gene (IT15) protein productNeuron, 14
- Publisher
- Springer Journals
- Copyright
- Copyright © 2001 by Nature Publishing Group
- Subject
- Biomedicine; Biomedicine, general; Human Genetics; Cancer Research; Agriculture; Gene Function; Animal Genetics and Genomics
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- DOI
- 10.1038/ng745
- Publisher site
- See Article on Publisher Site
Abstract
The cause of Huntington disease pathophysiology is unknown, but a major hypothesis suggests that toxicity arises from the cleavage and accumulation of amino-terminal fragments containing an expanded polyglutamine region. In evaluating huntingtin protein (HD) from human brain, transgenic animals and cells, we observed, unexpectedly, that mutant HD is more resistant to proteolysis than normal HD. The N-terminal cleavage fragments we observed arise from the processing of normal HD and are sequestered by full-length mutant HD. Our results support a model in which inhibition of proteolysis of mutant HD leads to aggregation and toxicity through the sequestering of important targets, including normal HD.
Journal
Nature Genetics – Springer Journals
Published: Oct 15, 2001