Tissue-specific proteolysis of Huntingtin (htt) in human brain: Evidence of enhanced levels of N- and C-terminal htt fragments in Huntington’s disease striatum

Mende-Mueller, Liane M.; Toneff, Thomas; Hwang, Shin-Rong; Chesselet, Marie-Francoise; Hook, Vivian Y. H.

doi:10.1523/jneurosci.21-06-01830.2001

Cited by 163Genetic Neurodegenerative DiseasesPrion Diseases and Protein MisfoldingLysosomal Storage Disorders Research

Tissue-specific proteolysis of Huntingtin (htt) in human brain: Evidence of enhanced levels of N- and C-terminal htt fragments in Huntington’s disease striatum

Open access

Mende-Mueller, Liane M., Toneff, Thomas, Hwang, Shin-Rong, Chesselet, Marie-Francoise, Hook, Vivian Y. H.·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-06-01830.2001PMC PMC6762596

Open this paper in CoChat — free account Open PDF

Abstract

Proteolysis of mutant huntingtin (htt) has been hypothesized to occur in Huntington's disease (HD) brains. Therefore, this in vivo study examined htt fragments in cortex and striatum of adult HD and control human brains by Western blots, using domain-specific anti-htt antibodies that recognize N- and C-terminal domains of htt (residues 181-810 and 2146-2541, respectively), as well as the 17 residues at the N terminus of htt. On the basis of the patterns of htt fragments observed, different "protease-susceptible domains" were identified for proteolysis of htt in cortex compared with striatum, suggesting that htt undergoes tissue-specific proteolysis. In cortex, htt proteolysis occurs within two different N-terminal domains, termed protease-susceptible domains "A" and "B." However, in striatum, a different pattern of fragments indicated that proteolysis of striatal htt occurred within a C-terminal domain termed "C," as well as within the N-terminal domain region designated "A". Importantly, striatum from HD brains showed elevated levels of 40-50 kDa N-terminal and 30-50 kDa C-terminal fragments compared with that of controls. Increased levels of these htt fragments may occur from a combination of enhanced production or retarded degradation of fragments. Results also demonstrated tissue-specific ubiquitination of certain htt N-terminal fragments in striatum compared with cortex. Moreover, expansions of the triplet-repeat domain of the IT15 gene encoding htt was confirmed for the HD tissue samples studied. Thus, regulated tissue-specific proteolysis and ubiquitination of htt occur in human HD brains. These results suggest that the role of huntingtin proteolysis should be explored in the pathogenic mechanisms of HD.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.21-06-01830.2001

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Unstable CAG repeats in exon 1 of HTT encode the N-terminal polyglutamine tract of the approximately 350 kDa, approximately 3100 amino acid huntingtin protein.
“The unstable CAG repeats in exon 1 of HTT encode the N-terminal polyglutamine tract of the ~350 kDa, ~3100 amino acid huntingtin protein [163].”
From The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases (2025) · cites this paper as [163]
The paper’s introductory passage (page unavailable) links an N-terminal huntingtin fragment containing CAG repeats to exon 1 and describes a polyglutamine expansion in mutant huntingtin. The analysis of triplet repeats also documents expanded CAG repeats in HD samples. The passages found do not establish the claimed approximately 350 kDa mass or approximately 3100-amino-acid length. (LLM, conf=0.83)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366 · see citing works
A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group.
Shah, M. A., Datson, N. A., Srinidhi, L., Stanton, V. P., MacDonald, M. E., Allard, M. W., Youngman, S., Am, F., Mott, R., Draths, K., et al. (1993) · Cell · Cited by 3,055 · see citing works
Aggregation of Huntingtin in Neuronal Intranuclear Inclusions and Dystrophic Neurites in Brain
DiFiglia, M., Sapp, E., Chase, K. O., Davies, S. W., Bates, G. P., Vonsattel, J., & D, N. A. M. (1997) · Science · doi:10.1126/science.277.5334.1990 · Cited by 2,849 · see citing works
Formation of Neuronal Intranuclear Inclusions Underlies the Neurological Dysfunction in Mice Transgenic for the HD Mutation
Davies, S. W., Turmaine, M., Cozens, B. A., DiFiglia, M., Sharp, A. H., Ross, C. A., Scherzinger, E., Wanker, E. E., Mangiarini, L., & Bates, G. P. (1997) · Cell · doi:10.1016/s0092-8674(00)80513-9 · Cited by 2,188 · see citing works
Huntingtin Acts in the Nucleus to Induce Apoptosis but Death Does Not Correlate with the Formation of Intranuclear Inclusions
Saudou, F., Finkbeiner, S. M., Devys, D., & Greenberg, M. E. (1998) · Cell · doi:10.1016/s0092-8674(00)81782-1 · Cited by 1,598 · see citing works
Huntington Disease
Vonsattel, J. P., & DiFiglia, M. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199805000-00001 · Cited by 1,305 · see citing works
Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease Mutation
Carter, R. J., Lione, L. A., Humby, T., Mangiarini, L., Mahal, A., Bates, G. P., Dunnett, S. B., & Morton, A. J. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-08-03248.1999 · Cited by 949 · see citing works
Nuclear and Neuropil Aggregates in Huntington’s Disease: Relationship to Neuropathology
Gutekunst, C.-A., Li, S.-H., Yi, H., Mulroy, J. S., Kuemmerle, S., Jones, R., Rye, D., Ferrante, R. J., Hersch, S. M., & Li, X.-J. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02522.1999 · Cited by 914 · see citing works
A YAC Mouse Model for Huntington’s Disease with Full-Length Mutant Huntingtin, Cytoplasmic Toxicity, and Selective Striatal Neurodegeneration
Hodgson, J., Agopyan, N., Gutekunst, C., Leavitt, B. R., LePiane, F. G., Singaraja, R. R., Smith, D. J., Bissada, N., McCutcheon, K. M., Nasir, J., et al. (1999) · Neuron · doi:10.1016/s0896-6273(00)80764-3 · Cited by 832 · see citing works
Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract
Goldberg, Y. P., Nicholson, D. W., Rasper, D., Kalchman, M. A., Koide, H., Graham, R. K., Bromm, M., Kazemi‐Esfarjani, P., Thornberry, N. A., Vaillancourt, J. P., et al. (1996) · Nature Genetics · doi:10.1038/ng0896-442 · Cited by 584 · see citing works
Caspase Cleavage of Gene Products Associated with Triplet Expansion Disorders Generates Truncated Fragments Containing the Polyglutamine Tract
Wellington, C. L., Ellerby, L., Hackam, A. S., Margolis, R. L., Trifiro, M. A., Singaraja, R. R., McCutcheon, K. M., Salvesen, G. S., Propp, S. S., Bromm, M., et al. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.15.9158 · Cited by 562 · see citing works
Morphometric Demonstration of Atrophic Changes in the Cerebral Cortex, White Matter, and Neostriatum in Huntington's Disease
de la Monte, S. M., Vonsattel, J., & Richardson, E. P. (1988) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198809000-00003 · Cited by 434 · see citing works
Huntingtin Is Ubiquitinated and Interacts with a Specific Ubiquitin-conjugating Enzyme
Kalchman, M. A., Graham, R. K., Xia, G., Koide, H., Hodgson, J. G., Graham, K. C., Goldberg, Y. P., Gietz, R. D., Pickart, C. M., & Hayden, M. R. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.32.19385 · Cited by 363 · see citing works
Inhibiting Caspase Cleavage of Huntingtin Reduces Toxicity and Aggregate Formation in Neuronal and Nonneuronal Cells
Wellington, C. L., Singaraja, R. R., Ellerby, L., Savill, J. M., Roy, S., Leavitt, B. R., Cattaneo, E. F., Hackam, A. S., Sharp, A. H., Thornberry, N. A., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001475200 · Cited by 358 · see citing works
Huntington's disease gene (IT15) is widely expressed in human and rat tissues
Li, S.-H., Schilling, G., Young, W. S., Li, X., Margolis, R. L., Stine, O. C., Wagster, M. V., Abbott, M. H., Franz, M. L., Ranen, N. G., et al. (1993) · Neuron · doi:10.1016/0896-6273(93)90127-d · Cited by 347 · see citing works
Mutant Huntingtin Expression in Clonal Striatal Cells: Dissociation of Inclusion Formation and Neuronal Survival by Caspase Inhibition
Kim, M., Lee, H.-S., Laforet, G. A., McIntyre, C., Martin, E. J., Chang, P., Kim, T. W., Williams, M. J., Reddy, P. H., Tagle, D., et al. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-03-00964.1999 · Cited by 305 · see citing works
Expression of Normal and Mutant Huntingtin in the Developing Brain
Bhide, P. G., Day, M., Sapp, E., Schwarz, C., Sheth, A. N., Kim, J., Young, A. B., Penney, J. B., Golden, J. A., D, N. A. M., et al. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-17-05523.1996 · Cited by 197 · see citing works
Recent Advances on the Pathogenesis of Huntington's Disease
Petersén, Å., Mani, K., & Brundin, P. (1999) · Experimental Neurology · doi:10.1006/exnr.1998.7006 · Cited by 158 · see citing works
Transgenic models of Huntington's disease
Bates, G. P. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.10.1633 · Cited by 109 · see citing works
Immunochemical characterization of carboxypeptidase B-like peptide-hormone-processing enzyme.
HOOK, V. Y. H., Mezey, É., Fricker, L. D., Pruss, R. M., Siegel, R. E., & Brownstein, M. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.14.4745 · Cited by 53 · see citing works
Self-citation
Molecular Studies Define the Primary Structure of α1-Antichymotrypsin (ACT) Protease Inhibitor in Alzheimer's Disease Brains
Hwang, S., Steineckert, B., Kohn, A. B., Palkovits, M., & HOOK, V. Y. H. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.3.1821 · Cited by 35 · see citing works
Self-citation
Molecular cloning reveals isoforms of bovine alpha 1-antichymotrypsin.
Hwang, S. R., Kohn, A. B., & HOOK, V. Y. H. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.20.9579 · Cited by 27 · see citing works
Self-citation
The Kunitz Protease Inhibitor Form of the Amyloid Precursor Protein (KPI/APP) Inhibits the Proneuropeptide Processing Enzyme Prohormone Thiol Protease (PTP)
HOOK, V. Y. H., Sei, C. A., Yasothornsrikul, S., Toneff, T., Kang, Y., Efthimiopoulos, S., Robakis, N. K. R. K., & Nostrand, W. V. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.5.3165 · Cited by 21 · see citing works
Self-citation
Evidence for Functional Localization of the Proenkephalin-Processing Enzyme, Prohormone Thiol Protease, to Secretory Vesicles of Chromaffin Cells
HOOK, V. Y. H., Noctor, S. C., Sei, C. A., Toneff, T., Yasothornsrikul, S., & Kang, Y. (1999) · Endocrinology · doi:10.1210/endo.140.8.6926 · Cited by 18 · see citing works
Self-citation
Homozygotes and heterozygotes for ciliary neurotrophic factor null alleles do not show earlier onset of Huntington's disease
Rubinsztein, D. C., Leggo, J., Chiano, M., Korn, S., Dodge, A., Norbury, G., Rosser, E. M., & Craufurd, D. (1997) · Neurology · doi:10.1212/wnl.49.3.890 · Cited by 6 · see citing works

Flagged first, then by citations

1 of the 26 references couldn’t be matched to a known paper.

Sorted by citations

Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R., & Finkbeiner, S. (2004) · Nature · doi:10.1038/nature02998 · Cited by 1,979 · see citing works
Molecular Mechanisms and Potential Therapeutical Targets in Huntington's Disease
Zuccato, C., Valenza, M., & Cattaneo, E. (2010) · Physiological Reviews · doi:10.1152/physrev.00041.2009 · Cited by 848 · see citing works
Sp1 and TAFII130 Transcriptional Activity Disrupted in Early Huntington's Disease
Dunah, A. W., Jeong, H., Griffin, A. M., Kim, Y., Standaert, D. G., Hersch, S. M., Mouradian, M. M., Young, A. B., Tanese, N., & Krainc, D. (2002) · Science · doi:10.1126/science.1072613 · Cited by 708 · see citing works
Normal huntingtin function: an alternative approach to Huntington's disease
Cattaneo, E. F., Zuccato, C., & Tartari, M. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1806 · Cited by 655 · see citing works
Targeting programmed cell death in neurodegenerative diseases
Vila, M., & Przedborski, S. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1100 · Cited by 545 · see citing works
Time course of early motor and neuropathological anomalies in a knock‐in mouse model of Huntington's disease with 140 CAG repeats
Menalled, L., Sison, J. D., Dragatsis, I., Zeitlin, S. O., & Chesselet, M. (2003) · The Journal of Comparative Neurology · doi:10.1002/cne.10776 · Cited by 528 · see citing works
Self-citation
Huntington’s Disease: Mechanisms of Pathogenesis and Therapeutic StrategiesPreprint
Jiménez-Sánchez, M., Licitra, F., Underwood, B. R., & Rubinsztein, D. C. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024240 · Cited by 512 · see citing works
Testosterone Reduction Prevents Phenotypic Expression in a Transgenic Mouse Model of Spinal and Bulbar Muscular Atrophy
Katsuno, M., Adachi, H., Kume, A., Li, M., Nakagomi, Y., Niwa, H., Sang, C., Kobayashi, Y., Doyu, M., & Sobue, G. (2002) · Neuron · doi:10.1016/s0896-6273(02)00834-6 · Cited by 474 · see citing works
The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system
Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., Palacín, M., & Zorzano, A. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi149 · Cited by 455 · see citing works
Proteases Acting on Mutant Huntingtin Generate Cleaved Products that Differentially Build Up Cytoplasmic and Nuclear Inclusions
Lunkes, A., Lindenberg, K. S., Ben-Haı̈em, L., Weber, C., Devys, D., Landwehrmeyer, G. B., Mandel, J., & Trottier, Y. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00602-0 · Cited by 413 · see citing works
Caspase Cleavage of Mutant Huntingtin Precedes Neurodegeneration in Huntington's Disease
Wellington, C. L., Ellerby, L., Gutekunst, C., Rogers, D., Warby, S. C., Graham, R. K., Loubser, O., Raamsdonk, J. M. V., Singaraja, R. R., Yang, Y., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-18-07862.2002 · Cited by 398 · see citing works
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
Kim, Y. J., Yi, Y., Sapp, E., Wang, Y., Cuiffo, B., Kegel, K. B., Qin, Z., D, N. A. M., & DiFiglia, M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.221451398 · Cited by 393 · see citing works
Dysregulation of gene expression in the R6/2 model of polyglutamine disease: parallel changes in muscle and brain
Luthi‐Carter, R. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.17.1911 · Cited by 364 · see citing works
Mouse models of Huntington's disease
Menalled, L., & Chesselet, M. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01884-8 · Cited by 311 · see citing works
Self-citation
Huntingtin Is Present in the Nucleus, Interacts with the Transcriptional Corepressor C-terminal Binding Protein, and Represses Transcription
Kegel, K. B., Meloni, A. R., Yi, Y., Kim, Y. J., Doyle, E., Cuiffo, B., Sapp, E., Wang, Y., Qin, Z., Chen, J. D., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m103946200 · Cited by 285 · see citing works
Antisense oligonucleotides in therapy for neurodegenerative disorders
Evers, M. M., Toonen, L. J. A., & van Roon‐Mom, W. (2015) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.03.008 · Cited by 284 · see citing works
Flanking sequences profoundly alter polyglutamine toxicity in yeast
Duennwald, M. L., Jagadish, S., Muchowski, P. J., & Lindquist, S. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604547103 · Cited by 282 · see citing works
Lessons from animal models of Huntington's disease
Rubinsztein, D. C. (2002) · Trends in Genetics · doi:10.1016/s0168-9525(01)02625-7 · Cited by 281 · see citing works
Mutant Huntingtin Causes Context-Dependent Neurodegeneration in Mice with Huntington's Disease
Yu, Z.-X., Li, S.-H., Evans, J., Pillarisetti, A., He, L., & Li, X. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-06-02193.2003 · Cited by 260 · see citing works
Autophagy regulates the processing of amino terminal huntingtin fragments
Qin, Z. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg346 · Cited by 250 · see citing works
Autophagy in neurons: a review.
Larsen, K. E., & Sulzer, D. L. (2002) · PubMed · doi:10.14670/hh-17.897 · Cited by 242 · see citing works
Specific caspase interactions and amplification are involved in selective neuronal vulnerability in Huntington's disease
Hermel, E., Gafni, J., Propp, S. S., Leavitt, B. R., Wellington, C. L., Young, J. E., Hackam, A. S., Logvinova, A. V., Peel, A. L., Chen, S. F., et al. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401358 · Cited by 227 · see citing works
Self-citation
Peptide Aggregation in Neurodegenerative Disease
Murphy, R. M. (2002) · Annual Review of Biomedical Engineering · doi:10.1146/annurev.bioeng.4.092801.094202 · Cited by 227 · see citing works
Huntington’s disease: from huntingtin function and dysfunction to therapeutic strategies
Borrell-Pagés, M., Zala, D., Humbert, S., & Saudou, F. (2006) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-006-6242-0 · Cited by 224 · see citing works
The biological function of the Huntingtin protein and its relevance to Huntington's Disease pathology.
Schulte, J., & Littleton, J. T. (2011) · PubMed · Cited by 203 · see citing works
Mutant Huntingtin Alters Retrograde Transport of TrkB Receptors in Striatal Dendrites
Liot, G., Zala, D., Pla, P., Mottet, G., Piel, M., & Saudou, F. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2033-12.2013 · Cited by 192 · see citing works
A Mutant Ataxin-3 Putative-Cleavage Fragment in Brains of Machado-Joseph Disease Patients and Transgenic Mice Is Cytotoxic above a Critical Concentration
Goti, D., Katzen, S. M., Mez, J. B., Kurtis, N., Kiluk, J., Ben-Haı̈em, L., Jenkins, N. A., Copeland, N. G., Kakizuka, A., Sharp, A. H., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2734-04.2004 · Cited by 191 · see citing works
Matrix Metalloproteinases Are Modifiers of Huntingtin Proteolysis and Toxicity in Huntington's Disease
Miller, J. P., Holcomb, J. L., Al‐Ramahi, I., de Haro, M., Gafni, J., Zhang, N., Kim, E. S., Sanhueza, M., Torcassi, C., Kwak, S., et al. (2010) · Neuron · doi:10.1016/j.neuron.2010.06.021 · Cited by 186 · see citing works
Wild‐type huntingtin protects neurons from excitotoxicity
Leavitt, B. R., Raamsdonk, J. M. V., Shehadeh, J., Fernandes, H. B., Murphy, Z., Graham, R. K., Wellington, C. L., Raymond, L. A., & Hayden, M. R. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03605.x · Cited by 184 · see citing works
Small Changes, Big Impact
Ehrnhoefer, D. E., Sutton, L. M., & Hayden, M. R. (2011) · The Neuroscientist · doi:10.1177/1073858410390378 · Cited by 184 · see citing works
Huntingtin contains a highly conserved nuclear export signal
Xia, J. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg156 · Cited by 175 · see citing works
The Role of Cathepsin D in the Pathogenesis of Human Neurodegenerative Disorders
Vidoni, C., Follo, C., Savino, M., Melone, M. A. B., & Isidoro, C. (2016) · Medicinal Research Reviews · doi:10.1002/med.21394 · Cited by 164 · see citing works
Huntingtin forms toxic NH2-terminal fragment complexes that are promoted by the age-dependent decrease in proteasome activity
Zhou, H., Cao, F., Wang, Z., Yu, Z.-X., Nguyen, H. P., Evans, J., Li, S.-H., & Li, X. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200306038 · Cited by 158 · see citing works
Huntington's disease: molecular basis of neurodegeneration
Rubinsztein, D. C., & Carmichael, J. (2003) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399403006549 · Cited by 154 · see citing works
Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity
Khoshnan, A., Ko, J., & Patterson, P. H. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022631799 · Cited by 151 · see citing works
Knock-in mouse models of Huntington’s disease
Menalled, L. (2005) · NeuroRx · doi:10.1602/neurorx.2.3.465 · Cited by 150 · see citing works
Huntington’s Disease and Mitochondria
Farshbaf, M. J., & Ghaedi, K. (2017) · Neurotoxicity Research · doi:10.1007/s12640-017-9766-1 · Cited by 148 · see citing works
Mutant Huntingtin N-terminal Fragments of Specific Size Mediate Aggregation and Toxicity in Neuronal Cells
Ratovitski, T., Guček, M., Jiang, H., Chighladze, E., Waldron, E., D'Ambola, J., Hou, Z., Liang, Y., Poirier, M. A., Hirschhorn, R. R., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m804813200 · Cited by 144 · see citing works
Huntingtin phosphorylation on serine 421 is significantly reduced in the striatum and by polyglutamine expansion in vivo
Warby, S. C., Chan, E. Y. W., Metzler, M., Gan, L., Singaraja, R. R., Crocker, S. F., Robertson, H. A., & Hayden, M. R. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi165 · Cited by 142 · see citing works
A role for autophagy in Huntington's disease
Croce, K. R., & Yamamoto, A. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.08.010 · Cited by 139 · see citing works
Characterization of Alternative Isoforms and Inclusion Body of the TAR DNA-binding Protein-43
Nishimoto, Y., Ito, D., Yagi, T., Nihei, Y., Tsunoda, Y., & Suzuki, N. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.022012 · Cited by 138 · see citing works
Increased huntingtin protein length reduces the number of polyglutamine-induced gene expression changes in mouse models of Huntington's disease
Chan, E. Y. W. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.17.1939 · Cited by 138 · see citing works
Inhibition of Calcineurin by FK506 Protects against Polyglutamine-Huntingtin Toxicity through an Increase of Huntingtin Phosphorylation at S421
Pardo, R., Colin, E., Régulier, E., Aebischer, P., Déglon, N., Humbert, S., & Saudou, F. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3706-05.2006 · Cited by 134 · see citing works
Ultrasensitive measurement of huntingtin protein in cerebrospinal fluid demonstrates increase with Huntington disease stage and decrease following brain huntingtin suppression
Southwell, A. L., Smith, S. E. P., Davis, T. R., Caron, N. S., Villanueva, E. B., Xie, Y., Collins, J. A., Ye, M. L., Sturrock, A., Leavitt, B. R., et al. (2015) · Scientific Reports · doi:10.1038/srep12166 · Cited by 109 · see citing works
Characterizing neutral genomic diversity and selection signatures in indigenous populations of Moroccan goats (Capra hircus) using WGS data
Benjelloun, B., Alberto, F. J., Streeter, I., Boyer, F., Coissac, É., Stucki, S., Benbati, M., Ibnelbachyr, M., Chentouf, M., Bechchari, A., et al. (2015) · Frontiers in Genetics · doi:10.3389/fgene.2015.00107 · Cited by 105 · see citing works
Huntingtin proteolysis releases non‐polyQ fragments that cause toxicity through dynamin 1 dysregulation
El‐Daher, M., Hangen, E., Bruyère, J., Poizat, G., Al‐Ramahi, I., Pardo, R., Bourg, N., Souquère, S., Mayet, C., Pierron, G., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490808 · Cited by 105 · see citing works
Ligand Promotes Intranuclear Inclusions in a Novel Cell Model of Spinal and Bulbar Muscular Atrophy
Walcott, J. L., & Merry, D. E. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m209466200 · Cited by 100 · see citing works
Mutant protein in Huntington disease is resistant to proteolysis in affected brain
Dyer, R. B., & McMurray, C. T. (2001) · Nature Genetics · doi:10.1038/ng745 · Cited by 92 · see citing works
Nuclear Localization of a Non-caspase Truncation Product of Atrophin-1, with an Expanded Polyglutamine Repeat, Increases Cellular Toxicity
Nucifora, F. C., Ellerby, L., Wellington, C. L., Wood, J. D., Herring, W. J., Sawa, A., Hayden, M. R., Dawson, V. L., Dawson, T. M., & Ross, C. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211224200 · Cited by 90 · see citing works
Detection of Alpha-Rod Protein Repeats Using a Neural Network and Application to Huntingtin
Palidwor, G., Shcherbinin, S., Huska, M. R., Raskó, T., Stelzl, U., Arumughan, A., Foulle, R., Porras, P., Sánchez‐Pulido, L., Wanker, E. E., et al. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000304 · Cited by 88 · see citing works
Role of proteolysis in polyglutamine disorders
Tarlac, V., & Storey, E. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10746 · Cited by 88 · see citing works
Calcium-dependent Cleavage of Endogenous Wild-type Huntingtin in Primary Cortical Neurons
Goffredo, D., Rigamonti, D., Tartari, M., Micheli, A. D., Verderio, C., Matteoli, M., Zuccato, C., & Cattaneo, E. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200353200 · Cited by 86 · see citing works
Comparative study of naturally occurring huntingtin fragments in Drosophila points to exon 1 as the most pathogenic species in Huntington's disease
Barbaro, B. A., Lukácsovich, T., Agrawal, N., Burke, J., Bornemann, D. J., Purcell, J. M., Worthge, S. A., Caricasole, A., Weiss, A., Song, W., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu504 · Cited by 83 · see citing works
Huntington's disease: Table 1
Davies, S., & Ramsden, D. B. (2001) · Molecular Pathology · doi:10.1136/mp.54.6.409 · Cited by 80 · see citing works
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79 · see citing works
Caspases in Huntington’s Disease
Sanchez-Mejia, R. O., & Friedlander, R. M. (2001) · The Neuroscientist · doi:10.1177/107385840100700604 · Cited by 66 · see citing works
N-Terminal Proteolysis of Full-Length Mutant Huntingtin in an Inducible PC12 Cell Model of Huntington’s Disease
Ratovitski, T., Nakamura, M., D'Ambola, J., Chighladze, E., Liang, Y., Wang, W., Graham, R. K., Hayden, M. R., Borchelt, D., Hirschhorn, R. R., et al. (2007) · Cell Cycle · doi:10.4161/cc.6.23.4992 · Cited by 65 · see citing works
Progressive phenotype and nuclear accumulation of an amino-terminal cleavage fragment in a transgenic mouse model with inducible expression of full-length mutant huntingtin
Tanaka, Y., Igarashi, S., Nakamura, M., Gafni, J., Torcassi, C., Schilling, G., Crippen, D., Wood, J., Sawa, A., Jenkins, N. A., et al. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.07.014 · Cited by 63 · see citing works
Huntington’s Disease: From Mutant Huntingtin Protein to Neurotrophic Factor Therapy
Sari, Y. (2011) · International Journal of Biomedical Science · doi:10.59566/ijbs.2011.7089 · Cited by 62 · see citing works
The use of transgenic and knock-in mice to study Huntington’s disease
Hickey, M. A., & Chesselet, M.-F. (2003) · Cytogenetic and Genome Research · doi:10.1159/000072863 · Cited by 60 · see citing works
Self-citation
Proteomics of Dense Core Secretory Vesicles Reveal Distinct Protein Categories for Secretion of Neuroeffectors for Cell−Cell Communication
Wegrzyn, J., Bark, S. J., Funkelstein, L., Mosier, C., Yap, A., Kazemi‐Esfarjani, P., Spada, A. R. L., Sigurdson, C. J., O’Connor, D. T., & HOOK, V. Y. H. (2010) · Journal of Proteome Research · doi:10.1021/pr1003104 · Cited by 57 · see citing works
Self-citation
Ataxin‐7 aggregation and ubiquitination in infantile SCA7 with 180 CAG repeats
Ansorge, O., Giunti, P., Michalik, A., Broeckhoven, C. V., Harding, B. N., Wood, N. W., & Scaravilli, F. (2004) · Annals of Neurology · doi:10.1002/ana.20230 · Cited by 57 · see citing works
The crystal structure of caspase-6, a selective effector of axonal degeneration
Baumgartner, R., Meder, G., Briand, C., Decock, A., D'Arcy, A., Hassiepen, U., Morse, R., & Renatus, M. (2009) · Biochemical Journal · doi:10.1042/bj20090540 · Cited by 55 · see citing works
Calmodulin Regulates Transglutaminase 2 Cross-Linking of Huntingtin
Zainelli, G. M., Ross, C. A., Troncoso, J. C., Fitzgerald, J. K., & Muma, N. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4424-03.2004 · Cited by 54 · see citing works
Sigma-2 Receptors—From Basic Biology to Therapeutic Target: A Focus on Age-Related Degenerative Diseases
Lizama, B. N., Kahle, J. S., Catalano, S. M., Caggiano, A. O., Grundman, M., & Hamby, M. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076251 · Cited by 51 · see citing works
Identification of a Karyopherin β1/β2 Proline-Tyrosine Nuclear Localization Signal in Huntingtin Protein
Desmond, C. R., Atwal, R. S., Xia, J., & Truant, R. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.412379 · Cited by 49 · see citing works
Cysteine Proteases Bleomycin Hydrolase and Cathepsin Z Mediate N-terminal Proteolysis and Toxicity of Mutant Huntingtin
Ratovitski, T., Chighladze, E., Waldron, E., Hirschhorn, R. R., & Ross, C. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.185348 · Cited by 48 · see citing works
A Mutant ataxin-3 fragment results from processing at a site N-terminal to amino acid 190 in brain of Machado–Joseph disease-like transgenic mice
Gould, V. F. C., Goti, D., Pearce, D., Gonzalez, G. A., Gao, H., de León, M. B., Jenkins, N. A., Copeland, N. G., Ross, C. A., & Brown, D. R. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.06.005 · Cited by 48 · see citing works
TBK1 phosphorylates mutant Huntingtin and suppresses its aggregation and toxicity in Huntington's disease models
Hegde, R. N., Chiki, A., Petricca, L., Martufi, P., Arbez, N., Mouchiroud, L., Auwerx, J. H., Landles, C., Bates, G. P., Singh‐Bains, M. K., et al. (2020) · The EMBO Journal · doi:10.15252/embj.2020104671 · Cited by 48 · see citing works
Polyglutamine Repeat Length-Dependent Proteolysis of Huntingtin
Sun, B., Fan, W., Balciunas, A. M., Cooper, J. K., Bitan, G., Steavenson, S., Denis, P. E., Young, Y., Adler, B. S., Daugherty, L., et al. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0539 · Cited by 47 · see citing works
Huntingtin is cleaved by caspases in the cytoplasm and translocated to the nucleus via perinuclear sites in Huntington's disease patient lymphoblasts
Sawa, A., Nagata, E., Sutcliffe, S. S., Dulloor, P., Cascio, M. B., Ozeki, Y., Roy, S., Ross, C. A., & Snyder, S. H. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.013 · Cited by 43 · see citing works
Huntingtin is degraded to small fragments by calpain after ischemic injury☆
Kim, M., Roh, J., Yoon, B. W., Kang, L., Kim, Y. J., D, N. A. M., & DiFiglia, M. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00132-8 · Cited by 41 · see citing works
Comparison of huntingtin proteolytic fragments in human lymphoblast cell lines and human brain
Toneff, T., Mende‐Mueller, L., Wu, Y. N., Hwang, S., Bundey, R. A., Thompson, L. M., Chesselet, M., & HOOK, V. Y. H. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00940.x · Cited by 38 · see citing works
Self-citation
Molecular Mechanisms Underlying Muscle Wasting in Huntington’s Disease
Bozzi, M., & Sciandra, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218314 · Cited by 36 · see citing works
Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1
Southwell, A. L., Bugg, C. W., Kaltenbach, L. S., Dunn, D., Butland, S. L., Weiss, A., Paganetti, P., Lo, D. C., & Patterson, P. H. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016676 · Cited by 35 · see citing works
Modulation of Mutant Huntingtin N-Terminal Cleavage and Its Effect on Aggregation and Cell Death
Juenemann, K., Weisse, C., Reichmann, D., Kaether, C., Calkhoven, C. F., & Schilling, G. (2010) · Neurotoxicity Research · doi:10.1007/s12640-010-9227-6 · Cited by 35 · see citing works
Ubiquilin/Dsk2 promotes inclusion body formation and vacuole (lysosome)-mediated disposal of mutated huntingtin
Chuang, K., Liang, F., Higgins, R. K., & Wang, Y. (2016) · Molecular Biology of the Cell · doi:10.1091/mbc.e16-01-0026 · Cited by 34 · see citing works
Assessing Polyglutamine Conformation in the Nucleating Event by Molecular Dynamics Simulations
Miettinen, M. S., Knecht, V., Monticelli, L., & Ignatova, Z. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp305065c · Cited by 31 · see citing works
Human Cathepsin V Protease Participates in Production of Enkephalin and NPY Neuropeptide Neurotransmitters
Funkelstein, L., Lu, W. D., Koch, B., Mosier, C., Toneff, T., Taupenot, L., O’Connor, D. T., Reinheckel, T., Peters, C., & HOOK, V. Y. H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.310607 · Cited by 31 · see citing works
Self-citation
Identification of Novel Alternative Splicing Events in the Huntingtin Gene and Assessment of the Functional Consequences Using Structural Protein Homology Modelling
Hughes, A. C., Mort, M. E., Elliston, L. A., Thomas, R. M., Brooks, S. P., Dunnett, S. B., & Jones, L. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.12.028 · Cited by 30 · see citing works
Altered Expression of Matrix Metalloproteinases and Their Endogenous Inhibitors in a Human Isogenic Stem Cell Model of Huntington's Disease
Naphade, S. B., Embusch, A., Madushani, K. L., Ring, K. L., & Ellerby, L. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00736 · Cited by 30 · see citing works
Mutant Huntingtin Protein Interaction Map Implicates Dysregulation of Multiple Cellular Pathways in Neurodegeneration of Huntington’s Disease
Podvin, S., Rosenthal, S. B., Poon, W. W. L., Wei, E., Fisch, K. M., & HOOK, V. Y. H. (2022) · Journal of Huntington s Disease · doi:10.3233/jhd-220538 · Cited by 27 · see citing works
Self-citation
Native Mutant Huntingtin in Human Brain
Sapp, E., Valencia, A., Li, X., D, N. A. M., Kegel, K. B., Vonsattel, J., Young, A. B., Wexler, N. S., & DiFiglia, M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.286609 · Cited by 27 · see citing works
The roles of proteolysis and nuclear localisation in the toxicity of the polyglutamine diseases. A review
Walsh, R., Storey, E., Stefani, D., Kelly, L. C., & Turnbull, V. J. (2005) · Neurotoxicity Research · doi:10.1007/bf03033775 · Cited by 26 · see citing works
Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars
Mačáková, M., Bohuslavová, B., Vochozková, P., Pavlok, A., Sedláčková, M., Vidinská, D., Vochyanova, K., Lišková, I., Valeková, I., Baxa, M., et al. (2016) · Neurodegenerative Diseases · doi:10.1159/000443665 · Cited by 24 · see citing works
Overview of Huntington's Disease Models: Neuropathological, Molecular, and Behavioral Differences
Rangel‐Barajas, C., & Rebec, G. V. (2018) · Current Protocols in Neuroscience · doi:10.1002/cpns.47 · Cited by 24 · see citing works
High-mobility group box 1 links sensing of reactive oxygen species by huntingtin to its nuclear entry
Son, S., Bowie, L. E., Maiuri, T., Hung, C. L.-K., Desmond, C. R., Xia, J., & Truant, R. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.001440 · Cited by 24 · see citing works
Protease Pathways in Peptide Neurotransmission and Neurodegenerative Diseases
HOOK, V. Y. H. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9047-7 · Cited by 24 · see citing works
Self-citation
Aggregate distribution in frontal and motor cortex in Huntington??s disease brain
van Roon‐Mom, W., Hogg, V. M., Tippett, L. J., & Faull, R. L. M. (2006) · Neuroreport · doi:10.1097/00001756-200604240-00022 · Cited by 23 · see citing works
Huntingtin cleavage product A forms in neurons and is reduced by gamma-secretase inhibitors
Kegel, K. B., Sapp, E., Alexander, J. S., Reeves, P., Bleckmann, D., Sobin, L., Masso, N., Valencia, A., Jeong, H., Krainc, D., et al. (2010) · Molecular Neurodegeneration · doi:10.1186/1750-1326-5-58 · Cited by 23 · see citing works
Huntingtin protein: A new option for fixing the Huntington's disease countdown clock
Caterino, M., Squillaro, T., Montesarchio, D., Giordano, A., Giancola, C., & Melone, M. A. B. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.03.009 · Cited by 23 · see citing works
Using Antibodies to Analyze Polyglutamine Stretches
Brooks, E., Arrasate, M., Cheung, K., & Finkbeiner, S. M. (2004) · Humana Press eBooks · doi:10.1385/1-59259-804-8:103 · Cited by 23 · see citing works
Transgenic minipig model of Huntington's disease exhibiting gradually progressing neurodegeneration
Ardan, T., Baxa, M., Levinská, B., Sedláčková, M., Nguyen, T. D., Klı́ma, J., Juhás, Š., Juhásová, J., Šmatlíková, P., Vochozková, P., et al. (2019) · Disease Models & Mechanisms · doi:10.1242/dmm.041319 · Cited by 22 · see citing works
Assessing average somatic CAG repeat instability at the protein level
Aviolat, H., Pinto, R. M., Godschall, E., Murtha, R., Richey, H. E., Sapp, E., Vodička, P., Wheeler, V. C., Kegel-Gleason, K. B., & DiFiglia, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-55202-x · Cited by 22 · see citing works
Molecular biology of Huntington's disease
McFarland, K. N., & Cha, J.-H. J. (2011) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52014-2.00003-3 · Cited by 21 · see citing works
Integration-independent Transgenic Huntington Disease Fragment Mouse Models Reveal Distinct Phenotypes and Life Span in Vivo
O’Brien, R., DeGiacomo, F., Holcomb, J., Bonner, A., Ring, K. L., Zhang, N., Zafar, K. S., Weiss, A., Lager, B., Schilling, B., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.623561 · Cited by 21 · see citing works
Epitope Mapping of Monoclonal Antibody 4C8 Recognizing the Protein Huntingtin
Cong, S., Pepers, B. A., Roos, R. A. C., van Ommen, G. B., & Dorsman, J. C. (2005) · Hybridoma · doi:10.1089/hyb.2005.24.231 · Cited by 20 · see citing works
Brain-penetrant PQR620 mTOR and PQR530 PI3K/mTOR inhibitor reduce huntingtin levels in cell models of HD
Singer, E., Walter, C., Fabbro, D., Rageot, D., Beaufils, F., Wymann, M. P., Rischert, N., Rieß, O., Hillmann, P., & Nguyen, H. P. (2019) · Neuropharmacology · doi:10.1016/j.neuropharm.2019.107812 · Cited by 20 · see citing works
A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies
Askeland, G., Rodinová, M., Štufková, H., Dosoudilova, Z., Baxa, M., Šmatlíková, P., Bohuslavová, B., Klempíř, J., Nguyen, T. D., Kuśnierczyk, A., et al. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.035949 · Cited by 19 · see citing works
Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age
Vidinská, D., Vochozková, P., Šmatlíková, P., Ardan, T., Klı́ma, J., Juhás, Š., Juhásová, J., Bohuslavová, B., Baxa, M., Valeková, I., et al. (2018) · Neurodegenerative Diseases · doi:10.1159/000488592 · Cited by 18 · see citing works

Comparison of huntingtin proteolytic fragments in human lymphoblast cell lines and human brain
Toneff, T., Mende‐Mueller, L., Wu, Y. N., Hwang, S., Bundey, R. A., Thompson, L. M., Chesselet, M., & HOOK, V. Y. H. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00940.x · Cited by 38 · see citing works
Self-citation
Huntingtin proteolysis in Huntington disease
Wellington, C. L., Ellerby, L., Leavitt, B. R., Roy, S., Nicholson, D. W., & Hayden, M. R. (2003) · Clinical Neuroscience Research · doi:10.1016/s1566-2772(03)00055-0 · Cited by 12 · see citing works
B07 Analysis of huntingtin protein fragments in post mortem human Huntington's disease brain tissue
Schut, M. H., Bullock, J. Y., Patassini, S., Kim, E., Waldvogel, H. J., Pepers, B. A., den Dunnen, J., van Ommen, G. B., Faull, R. L. M., & van Roon-Mom, W. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303524.23 · Cited by 1 · see citing works
Mutant protein in Huntington disease is resistant to proteolysis in affected brain
Dyer, R. B., & McMurray, C. T. (2001) · Nature Genetics · doi:10.1038/ng745 · Cited by 92 · see citing works
Proteolysis of Mutant Huntingtin Produces an Exon 1 Fragment That Accumulates as an Aggregated Protein in Neuronal Nuclei in Huntington Disease
Landles, C., Sathasivam, K., Weiss, A., Woodman, B., Moffitt, H., Finkbeiner, S. M., Sun, B., Gafni, J., Ellerby, L., Trottier, Y., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.075028 · Cited by 328 · see citing works

Authors: Mende-Mueller, L. M., Toneff, T., Hwang, S.-R., Chesselet, M.-F., & Hook, V. Y. H.
Affiliations: Buck Institute for Research on Aging (US)
ORCID: Hook, Vivian Y. H.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-03-15
Volume: 21
Issue: 6
Pages: 1830-1837
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-06-01830.2001
PMC: PMC6762596
OpenAlex: W2101847922
Cited by: 163
References: 26
Citations by year: 2026: 1 · 2025: 7 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 3 · 2019: 10 · 2018: 9 · 2017: 4 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 3 · 2012: 8
FWCI: 5.40
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Hereditary Disease Foundation
National Institute of Mental Health (MH.NS 31862)
National Cancer Institute (R01CA092126)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords: huntingtin, Huntington's disease, proteolysis, striatum, cerebral cortex, N-terminal fragment, C-terminal fragment, ubiquitination, trinucleotide repeat expansion, IT15 gene
MeSH terms: Huntingtin Protein, Aged, Antibody Specificity, Brain, Cerebral Cortex, Corpus Striatum, Humans, Huntington Disease, Middle Aged, Nerve Tissue Proteins, Nuclear Proteins, Organ Specificity, Peptide Fragments, Peptide Hydrolases, Putamen, Ubiquitins, Blotting, Western, Polymerase Chain Reaction, Protein Structure, Tertiary, Trinucleotide Repeat Expansion

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Tissue-specific proteolysis of Huntingtin (htt) in human brain: Evidence of enhanced levels of N- and C-terminal htt fragments in Huntington’s disease striatum

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks