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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.
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“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
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Huntingtin disrupts lipid bilayers in a polyQ-length dependent manner
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Jin, Y. N., & Johnson, G. V. W. (2010) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-010-9286-7 · Cited by 80
“intraneuronal aggregates containing mHtt were first discovered in the brain of HD patients and HD mouse models it was suggested that they had a causative role (Davies et al. 1997; DiFiglia et al. 1997; Scherzinger et al. 1997).”
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“Such an expansion of polyQ repeats in the mutant proteins leads to the formation of intracellular aggregates (Scherzinger et al., 1997).”
BackgroundMethylene blue fails to inhibit Tau and polyglutamine protein dependent toxicity in zebrafish
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“This assay was 6 initially developed to investigate amyloid formation of huntingtin in in vitro 7 aggregation assays (Scherzinger et al. 1997), but it can also be used to detect 8 aggregates in yeast cell lysates.”
MethodHuman embryonic stem cell models of Huntington disease
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“, 1997) and mutant huntingtin in HD (Scherzinger et al., 1997).”
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Self-citationMukai, H., Isagawa, T., Goyama, E., Tanaka, S., Bence, N., Tamura, A., Ono, Y., & Kopito, R. R. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409283102 · Cited by 75
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“…fibrillization into amyloid-like aggregates, consistent with the prediction outlined above, has been found in in vitro experiments by Wanker and coworkers using glutathione S-transferase (GST) fusion proteins of an N-terminal fragment of huntingtin (htt Exon 1) (Scherzinger et al., 1997).”
ResultNuclear Aggresomes Form by Fusion of PML-associated Aggregates
Fu, L., Gao, Y., Tousson, A., Shah, A., Chen, T.-L. L., Vertel, B. M., & Sztul, E. S. (2005) · Molecular Biology of the Cell · doi:10.1091/mbc.e05-01-0019 · Cited by 73
“Proteins deposited within aggresomes are largely detergent insoluble (Ward et al., 1995; Scherzinger et al., 1997; Garcia-Mata et al., 1999; Kopito, 2000).”
BackgroundTransgenic models of Huntington's disease.
Sathasivam, K., Hobbs, C., Mangiarini, L., Mahal, A., Turmaine, M., Doherty, P., Davies, S., & Bates, G. (1999) · Human Molecular Genetics · doi:10.1098/rstb.1999.0447 · Cited by 133
Self-citationTransgenic Mice in the Study of Polyglutamine Repeat Expansion Diseases
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“This is supported by the demonstration that it is necessary to remove the GST-tag from an exon 1 htt fusion protein containing 51 glutamines before aggregation can take place (56).”
BackgroundInfluentialSelf-citationCooper, A. J. L., Sheu, K. R., Burke, J. R., Strittmatter, W. J., Gentile, V., Peluso, G., & Blass, J. P. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0720889.x · Cited by 72
“In all these disorders, progressive impairment of coordination and/or motor neuron degeneration is associated with variable mental symptoms (Paulson and Fishbeck, 1996; Lunkes and Mandel, 1997; Scho¨ls et al., 1997).”
BackgroundHuntingtin: a single bait hooks many species
Gusella, J. F., & MacDonald, M. E. (1998) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(98)80071-8 · Cited by 72
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“Wanker and coworkers performed ultrastructural analysis of these abnormal structures, and revealed the presence of amyloid-like fibrillar structures, not only in the aggregates formed in vitro, but also in the inclusion bodies in the brains of the transgenic mice models [37].”
BackgroundNeurotoxic protein oligomerisation associated with polyglutamine diseases
Hands, S. L., & Wyttenbach, A. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0703-0 · Cited by 72
Marchut, A. J., & Hall, C. (2006) · Biophysical Journal · doi:10.1529/biophysj.105.079269 · Cited by 67
“(39) used electron microscopy to study the structure of aggregates formed from Huntington containing an expanded polyglutamine tract and found that these aggregates are fibrillar.”
BackgroundMechanisms of Neurodegenerative Disorders
Wolozin, B. L., & Behl, C. (2000) · Archives of Neurology · doi:10.1001/archneur.57.6.793 · Cited by 70
Sontag, E. M., Joachimiak, Ł. A., Tan, Z., Tomlinson, A. A. G., Housman, D. E., Glabe, C. G., Potkin, S. G., Frydman, J., & Thompson, L. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222663110 · Cited by 72
Polyglutamine Expansion in Ataxin-3 Does Not Affect Protein Stability
Chow, M. K. M., Ellisdon, A. M., Cabrita, L. D., & Bottomley, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405799200 · Cited by 70
The emerging role of the first 17 amino acids of huntingtin in Huntington’s disease
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“It has been demonstrated, biochemically and biophysically, that htt fragments containing expanded polyQ tracts readily form detergent-insoluble protein aggregates with characteristics of amyloid fibrils (28, 34).”
BackgroundAggregation Formation in the Polyglutamine Diseases: Protection at a Cost?
Todd, T. W., & Lim, J. (2013) · Molecules and Cells · doi:10.1007/s10059-013-0167-x · Cited by 73
“…similarities including progressive neurodegeneration in a disease-specific subset of neurons and the presence of insoluble protein aggregates (reviewed by Bauer and Nukina, 2009; Gusella and MacDonald, 2000; Orr and Zoghbi, 2007; Shao and Diamond, 2007; Takahashi et al., 2008; Watson et al., 2012).”
BackgroundOligomeric and polymeric aggregates formed by proteins containing expanded polyglutamine
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Inhibition of Polyglutamine Aggregation in R6/2 HD Brain Slices—Complex Dose–Response Profiles
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Self-citationProtein misfolding inside cells: The case of huntingtin and Huntington's disease
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“for identifying the different conformations of huntingtin in cells other than from ex situ experiments such as SDS-solubility assays (29) or antibodies directed against conformation-specific epitopes (30–32).”
BackgroundY-27632 improves rotarod performance and reduces huntingtin levels in R6/2 mice
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Proteasome degrades soluble expanded polyglutamine completely and efficiently
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“Indeed, intracellular polyglutamine aggregates have been observed in patient tissue (DiFiglia et al., 1997; Paulson et al., 1997) and reproduced both in vitro (Scherzinger et al., 1997) and in cellular and animal models (Burright et al., 1995; Davies et al., 1997; Paulson et al., 1997).”
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Protein aggregates and dementia: is there a common toxicity?
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Generalization of the Prion Hypothesis to Other Neurodegenerative Diseases: An Imperfect Fit
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“Extended polyglutamine tracts in recombinant proteins were observed to aggregate spontaneously and form amyloid fibrils ultrastructurally similar to amyloid-β (Scherzinger et al. 1997).”
BackgroundSignaling and other functions of lipids in autophagy: a review
Soto-Avellaneda, A., & Morrison, B. E. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01389-2 · Cited by 71
Oligonucleotide-based strategies to combat polyglutamine diseases
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Pathological and functional amyloid formation orchestrated by the secretory pathway
Huff, M. E., Balch, W. E., & Kelly, J. W. (2003) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2003.10.010 · Cited by 68
“Proteins deposited intracellularly include a-synuclein in Parkinson’s disease [4,5], Huntingtin in Huntington’s disease [6,7], Cu/Zn superoxide dismutase in some amyotrophic lateral sclerosis cases (Lou Gehrig’s disease) [8–10] and tau associated with Alzheimer’s disease (AD) [11–13].”
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Stochastic kinetics of intracellular huntingtin aggregate formation
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“Regardless of whether the aggregates are themselves toxic, their formation is strongly correlated with polyglutamine length and httex1 concentration in the same fashion as cell death in cultur”
BackgroundThe Role of Intrinsically Unstructured Proteins in Neurodegenerative Diseases
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Assessing mutant huntingtin fragment and polyglutamine aggregation by atomic force microscopy
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“A battery of tests—designed to assess motor function, electrophysiology of medium-sized spiny neurons (MSNs), previously shown to be altered in HD mouse models (Carter et al. 1999; Cepeda et al. 2003, 2007; Cummings et al. 2009; Davies et al. 1997; Scherzinger et al. 1997; Starling et al. 2005), inclusion formation, a…”
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Tissue Transglutaminase Does Not Contribute to the Formation of Mutant Huntingtin Aggregates
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“In vitro, polyglutamine constructs form b -sheets that are held together by hydrogen bonds (Perutz et al., 1994; Stott et al., 1995; Scherzinger et al., 1997).”
BackgroundInfluentialCooper, A. J. L., Jeitner, T. M., Gentile, V., & Blass, J. P. (2002) · Neurochemistry International · doi:10.1016/s0197-0186(01)00058-4 · Cited by 64
Insights into the Aggregation Mechanism of PolyQ Proteins with Different Glutamine Repeat Lengths
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Widespread remodeling of proteome solubility in response to different protein homeostasis stresses
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“Indeed, mutant huntingtin fragment forms amyloid-like fibrils in vitro ( Scherzinger et al., 1997; Huang et al., 1998) and Congo-red-positive aggregate has been isolated from HD brain using a filter-trap assay (Huang et al., 1998).”
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Are there multiple pathways in the pathogenesis of Huntington'sdisease?
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“Alterations in nuclear function caused by targeting of the cleaved or fully intact protein to the nucleus, with the tendency of huntingtin to form ¢laments (Perutz et al. 1994; Scherzinger et al. 1997), are especially pronounced in patients with juvenile-onset Huntingtons' disease and even pre-empt changes in the cyto…”
BackgroundBulone, D., Masino, L., Thomas, D. J., Biagio, P. L. S., & Pastore, A. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000111 · Cited by 62
“studies have shown that polyQ aggregation depends on protein concentration, repeat-length, and time and that it occurs with a nucleation-dependent mechanism”
BackgroundSmall Molecule Inducers of Heat-Shock Response Reduce polyQ-Mediated Huntingtin Aggregation
Herbst, M., & Wanker, E. E. (2007) · Neurodegenerative Diseases · doi:10.1159/000101849 · Cited by 63
Self-citationPolyglutamine Aggregation in Huntington Disease: Does Structure Determine Toxicity?
Hoffner, G., & Djian, P. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8932-1 · Cited by 64
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“, small oligomers and fibrils, have been described as potentially pathogenic (Nucifora et al., 2012; Pieri et al., 2012; Scherzinger et al., 1997), the mHTT species that exhibit seeding activity in vivo still need to be pinpointed.”
BackgroundSelf-citationHuntingtin aggregation monitored by dynamic light scattering
Georgalis, Y., STARIKOV, E. B., Hollenbach, B., Lurz, R., Scherzinger, E., Saenger, W., Lehrach, H. R., & Wanker, E. E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6118 · Cited by 62
Self-citationSaitoh, Y., Fujikake, N., Okamoto, Y., Popiel, H. A., Hatanaka, Y., Ueyama, M., Suzuki, M., Gaumer, S., Murata, M., Wada, K., et al. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.590281 · Cited by 55
“PolyQ proteins are prone to misfold, oligomerize, and form aggregates and eventually accumulate as inclusion bodies in affected neurons (2, 3).”
BackgroundSenatorov, V. V., Charles, V., Reddy, P. H., Tagle, D., & Chuang, D. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(02)00013-1 · Cited by 61
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Alternative processing of human HTT mRNA with implications for Huntington’s disease therapeutics
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“9,10 In recent years various therapeutic strategies have been devised to combat Huntington’s disease.”
Self-citationKettern, N., Rogon, C., Limmer, A., Schild, H., & Höhfeld, J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016398 · Cited by 60
“DALIS we adopted a filter trap assay, previously used to verify pathogenic protein aggregation in neuronal cells [33].”
MethodWang, J. K. T., Langfelder, P., Horvath, S., & Palazzolo, M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00149 · Cited by 61
“The N terminal fragments of mutant HTT (mHTT) is prone to misfolding and aggregation (Scherzinger et al., 1997; Poirier et al., 2002; Thakur et al., 2009), a feature shared with pathogenic proteins implicated in other neurodegenerative diseases.”
BackgroundSahoo, B., Arduini, I., Drombosky, K. W., Kodali, R. B., Sanders, L. H., Greenamyre, J. T., & Wetzel, R. B. (2016) · PLoS ONE · doi:10.1371/journal.pone.0155747 · Cited by 59
Proteostasis of Huntingtin in Health and Disease
Koyuncu, S., Fatima, A., Gutiérrez-García, R., & Vı́lchez, D. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18071568 · Cited by 61
“These mutations expand the polyglutamine stretch (polyQ) of the N-terminal domain of the HTT protein, resulting in proteotoxicity and protein aggregation [1,7,8].”
BackgroundProtein aggregation in cell biology: An aggregomics perspective of health and disease
Cox, D., Raeburn, C., Sui, X., & Hatters, D. M. (2018) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2018.05.003 · Cited by 60
Insoluble TATA-binding protein accumulation in Huntington’s disease cortex
van Roon‐Mom, W., Reid, S. J., Jones, A. L., MacDonald, M. E., Faull, R. L. M., & Snell, R. G. (2002) · Molecular Brain Research · doi:10.1016/s0169-328x(02)00450-3 · Cited by 59
Chow, M. K. M., Paulson, H. L., & Bottomley, S. (2003) · Journal of Molecular Biology · doi:10.1016/j.jmb.2003.08.064 · Cited by 59
The mouse SCA2 gene: cDNA sequence, alternative splicing and protein expression.
Nechiporuk, T., Huynh, D., Figueroa, K., Sahba, S., Nechiporuk, A., & Pulst, S. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.8.1301 · Cited by 66
Tanaka, K., Showguchi-Miyata, J., Miyamoto, N., & Ikeda, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310726200 · Cited by 58
Dorsman, J. C. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.13.1487 · Cited by 58
Targeted protein degradation in drug development: Recent advances and future challenges
Song, J. H., Hu, M., Zhou, J., Xie, S., Li, T., & Li, Y. (2023) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2023.115839 · Cited by 56
Kvam, E., Nannenga, B. L., Wang, M. S., Jia, Z., Sierks, M. R., & Messer, A. C. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005727 · Cited by 60
“Following standard protocols for generating httex1 fibrils containing an expanded polyglutamine tract (51Q) typical of adult HD onset [8], mutant httex1 fibrils were deposited onto freshly cleaved mica for surface height analyses by AFM.”
BackgroundMethodInfluentialProtein aggregation in Huntington’s disease
Hoffner, G., & Djian, P. (2002) · Biochimie · doi:10.1016/s0300-9084(02)01398-6 · Cited by 57
Abdullah, A. A. R. (1998) · Human Molecular Genetics · doi:10.1093/hmg/7.3.379 · Cited by 57
“The presence of the 75 kDa fragment in nuclear extracts is in keeping with the recent observation of inclusion bodies containing Gln-expanded protein in brain nuclei of the HD transgenic mouse and SCA3 patients (17,31, 32 ).”
ResultRajput, A. H., Rajput, A. H., Lang, A. E., Kumar, R., Uitti, R. J., Couteur, D. G. L., McCann, S. J., Bêcher, M. W., Ross, C. A., & Hardie, R. J. (1998) · Movement Disorders · doi:10.1002/mds.870130520 · Cited by 57
Ishiguro, T., Ishikawa, K., Takahashi, M., Obayashi, M., Amino, T., Sato, N. J., Sakamoto, M., Fujigasaki, H., Tsuruta, F., Dolmetsch, R. E., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0630-0 · Cited by 56
“To clarify the Cav2.1 expression pattern in more detail, subcellular fractionations were performed at 4C, as previously described [ 40 ] (Fig. 2). Brain samples (0.5 g each of either, cerebellum, occipital cortex, or thalamus) were homogenized in ten volumes of buffer containing 0.32 M sucrose, 20 mM HEPES homogenizat…”
MethodInfluentialDı́az-Hernández, M., Moreno‐Herrero, F., Gómez‐Ramos, P., Morán, M. A., Ferrer, I., Baró, A. M., Ávila, J., Hernández, F., & Lucas, J. J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2365-04.2004 · Cited by 56
“Aggregates have been implicated as the trigger for neurodegeneration, because both aggregates and pathogenicity are caused by the same polyQ length threshold (Scherzinger et al., 1997).”
BackgroundHigh-Capacity Adenoviral Vector-Mediated Reduction of Huntingtin Aggregate Load In Vitro and In Vivo
Huang, B., Schiefer, J., Saß, C., Landwehrmeyer, G. B., Kosinski, C. M., & Kochanek, S. (2007) · Human Gene Therapy · doi:10.1089/hum.2006.160 · Cited by 57
Toward an Understanding of Polyglutamine Neurodegeneration
Paulson, H. L. (2000) · Brain Pathology · doi:10.1111/j.1750-3639.2000.tb00263.x · Cited by 56
“Moreover, purified recombinant polyglutamine protein aggregates into amyloid-like fibrils in a concentration- and repeat length-dependent manner (37).”
BackgroundSchlumpberger, M., Wille, H., Baldwin, M. A., Butler, D. A., Herskowitz, I., & Prusiner, S. B. (2000) · Protein Science · doi:10.1110/ps.9.3.440 · Cited by 56
“Furthermore, amyloid-like fiber formation has been shown for N-terminal parts of Huntingtin with extended polyglutamine repeats after proteolytic cleavage of GST fusion proteins~Scherzinger et al., 1997, 1999!.”
BackgroundCoelho, P., Fão, L., Mota, S. I., & Rego, A. C. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101667 · Cited by 62
Polyglutamine Toxicity Is Controlled by Prion Composition and Gene Dosage in Yeast
Gong, H., Romanova, N. V., Allen, K., Chandramowlishwaran, P., Gokhale, K., Newnam, G. P., Mieczkowski, P. A., Sherman, M. Y., & Chernoff, Y. O. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002634 · Cited by 55
The huntingtin inclusion is a dynamic phase-separated compartment
Aktar, F., Burudpakdee, C., Polanco, M., Pei, S., Swayne, T. C., Lipke, P. N., & Emtage, L. (2019) · Life Science Alliance · doi:10.26508/lsa.201900489 · Cited by 56
“…cleavage to release an N-terminal fragment containing the polyglutamine region (Becher et al, 1998; Thomas et al, 1998; Landles et al, 2010), and this fragment forms inclusions in individuals affected by Huntington’s disease (Scherzinger et al, 1997; Huang et al, 1998; McGowan et al, 2000).”
BackgroundKushwah, N. S., Jain, V., & Yadav, D. (2020) · Biomolecules · doi:10.3390/biom10010132 · Cited by 54
“Huntington disease is caused by mutation in gene encoding the protein huntingtin1 [61].”
BackgroundGeneration of New Isogenic Models of Huntington’s Disease Using CRISPR-Cas9 Technology
Dabrowska, M., Ciołak, A., Kozłowska, E., Fiszer, A., & Olejniczak, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051854 · Cited by 54
Amyloid Oligomer Neurotoxicity, Calcium Dysregulation, and Lipid Rafts
Malchiodi‐Albedi, F., Paradisi, S., Matteucci, A., Frank, C., & Diociaiuti, M. (2011) · International Journal of Alzheimer s Disease · doi:10.4061/2011/906964 · Cited by 55
Protein aggregation, cardiovascular diseases, and exercise training: Where do we stand?
Gouveia, M., Xia, K., Colón, W., Vieira, S. I., & Ribeiro, F. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.07.005 · Cited by 54
Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation
Rodríguez-González, C., Lin, S., Arkan, S., & Hansen, C. (2020) · Scientific Reports · doi:10.1038/s41598-020-65046-5 · Cited by 54
Hishikawa, N., Niwa, J.-I., Doyu, M., Ito, T., Ishigaki, S., Hashizume, Y., & Sobue, G. (2003) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63688-7 · Cited by 54
“Cellulose acetate membranes usually bind protein very poorly and are used to filter high-molecular weight structures from complex mixtures.(35) Thus we investiTable 1.”
Protein aggregation in Huntington’s and Parkinson’s disease: implications for therapy
Wanker, E. E. (2000) · Molecular Medicine Today · doi:10.1016/s1357-4310(00)01761-5 · Cited by 54
Self-citation
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
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