The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
Huntingtin-Encoded Polyglutamine Expansions Form Amyloid-like Protein Aggregates In Vitro and In Vivo
Open accessAbstract
The mechanism by which an elongated polyglutamine sequence causes neurodegeneration in Huntington's disease (HD) is unknown. In this study, we show that the proteolytic cleavage of a GST-huntingtin fusion protein leads to the formation of insoluble high molecular weight protein aggregates only when the polyglutamine expansion is in the pathogenic range. Electron micrographs of these aggregates revealed a fibrillar or ribbon-like morphology, reminiscent of scrapie prions and beta-amyloid fibrils in Alzheimer's disease. Subcellular fractionation and ultrastructural techniques showed the in vivo presence of these structures in the brains of mice transgenic for the HD mutation. Our in vitro model will aid in an eventual understanding of the molecular pathology of HD and the development of preventative strategies.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Mutant huntingtin, however, has a propensity to aggregate in the nucleus and in the cytoplasm, which is reported both in human HD patients and in animal models, in dendrites as well as in dendritic spines (Di-Figlia et al., 1997;Scherzinger et al., 1997;Gutekunst et al., 1999;Lunkes et al., 2002).”
From Dendritic Spine Instability Leads to Progressive Neocortical Spine Loss in a Mouse Model of Huntington's Disease (2013) · cites this paper as Scherzinger et al., 1997
Citations
Cites
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.9.4350 · Cited by 53,218
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366
Smith, D. B., & Johnson, K. S. (1988) · Gene · doi:10.1016/0378-1119(88)90005-4 · Cited by 5,844
Mangiarini, L., Sathasivam, K., Seller, M., Cozens, B., Harper, A., Hetherington, C., Lawton, M., Trottier, Y., Lehrach, H., Davies, S. W., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81369-0 · Cited by 3,073
Self-citationNeuropathological Classification of Huntingtonʼs Disease
VONSATTEL, J.-P., MYERS, R. H., STEVENS, T. J., FERRANTE, R. J., BIRD, E. D., & RICHARDSON, E. P. (1985) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-198511000-00003 · Cited by 2,227
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
Self-citationJarrett, J. T., & Lansbury, P. T. (1993) · Cell · doi:10.1016/0092-8674(93)90635-4 · Cited by 2,178
Amyloid Deposits and Amyloidosis
Glenner, G. G. (1980) · New England Journal of Medicine · doi:10.1056/nejm198006053022305 · Cited by 1,780
Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases.
Perutz, M. F., Johnson, T., Suzuki, M., & Finch, J. T. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5355 · Cited by 1,060
Scrapie prions aggregate to form amyloid-like birefringent rods
Prusiner, S. B., McKinley, M. P., Bowman, K. A., Bolton, D. C., Bendheim, P. E., Groth, D., & Glenner, G. G. (1983) · Cell · doi:10.1016/0092-8674(83)90168-x · Cited by 1,052
Research works printed but not linked: 2
- Harper, P.S. (1991). Huntington's disease, Edition 22. P.S. Harper, ed. (London: W.B. Saunders Co., Ltd).
- Roizin, 1979, Neuronal nuclear-cytoplasmic changes in Huntington's chorea, Adv. Neurol., 23, 95
Cited by
Sorted by citations
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. P., & Aronin, N. (1997) · Science · doi:10.1126/science.277.5334.1990 · Cited by 2,439
Self-citationDavies, 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
“It may have been expected that asof the HD gene carrying (CAG)53 can form aggregates in the R6 transgene protein contains only the N-terminalvitro may support a homodimerization model for the 3% of htt, the transgenes would represent a genericmutant protein (Scherzinger et al., 1997).”
BackgroundSelf-citationInclusion 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
Apoptosis in the nervous system
Yuan, J., & Yankner, B. A. (2000) · Nature · doi:10.1038/35037739 · Cited by 1,882
Conway, K. A., Lee, S., Rochet, J., Ding, T. T., Williamson, R. E., & Lansbury, P. T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.571 · Cited by 1,559
Metadata
- Authors
- Scherzinger, E., Lurz, R., Turmaine, M., Mangiarini, L., Hollenbach, B., Hasenbank, R., Bates, G. P., Davies, S. W., Lehrach, H., & Wanker, E. E.
- Affiliations
- Max Planck Institute for Molecular Genetics (DE)
- University College London (GB)
- Guy's Hospital (GB)
- Corresponding author
- Wanker, Erich E
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-08
- Volume
- 90
- Issue
- 3
- Pages
- 549-558
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2079250951
- Cited by
- 1,291
- References
- 42
- Citations by year
- 2026: 17 · 2025: 31 · 2024: 23 · 2023: 23 · 2022: 24 · 2021: 37 · 2020: 55 · 2019: 44 · 2018: 49 · 2017: 43 · 2016: 34 · 2015: 32 · 2014: 43 · 2013: 38 · 2012: 52
- FWCI
- 25.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Huntington's disease, polyglutamine expansion, huntingtin, protein aggregation, amyloid-like aggregates, proteolytic cleavage, GST fusion protein, neurodegeneration, transgenic mouse model, fibril morphology, amyloid-beta
- MeSH terms
- Huntingtin Protein, Amino Acid Sequence, Amyloid, Animals, Base Sequence, Brain, Cell Nucleus, Exons, Glutathione Transferase, Humans, Huntington Disease, Kidney, Mice, Transgenic, Molecular Sequence Data, Nerve Tissue Proteins, Nuclear Proteins, Recombinant Fusion Proteins, Polymerase Chain Reaction, DNA Primers, Macromolecular Substances, Mice
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
