Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua
Open accessAbstract
Gentle exercise can ameliorate disease severity in a mouse model of a fatal neurodegenerative disease.
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Neurodegeneration in SCA1 results from a gain of endogenous functions mediated by polyglutamine-expanded mutant ATXN1 and from a concurrent partial loss of the beneficial functions of wild-type ATXN1.
“in SCA1 results from a gain of endogenous functions mediated by the polyglutamine-expanded mutant ATXN1, and from a concurrent partial loss of the beneficial functions of wild-type ATXN1 (Lim et al., 2008; Crespo-Barreto et al., 2010; Fryer et al., 2011).”
From Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1 (2013) · cites this paper as Fryer et al., 2011
The paper’s discussion (page unavailable in our copy) identifies a gain-of-function mechanism as the driver of SCA1 toxicity. It also reports a concurrent partial loss of Capicua’s normal repressor activity, but does not establish that the concurrent loss is of beneficial wild-type ATXN1 functions as the claim states. (LLM, conf=0.86)
Experimental — accuracy not yet measuredATXN1 protein binds to CIC family transcription factors and regulates transcription of target genes in vitro and in vivo.
“The ATXN1 protein binds to the CIC family of transcription factors and regulates the transcription of target genes in vitro in cell culture systems (Lam et al., 2006) as well as in vivo in mice (Crespo-Barreto et al., 2010; Fryer et al., 2011).”
From Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1 (2013) · cites this paper as Fryer et al., 2011
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Cites
Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1
Orr, H. T., Chung, M.-Y., Banfi, S., Kwiatkowski, T. J., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., & Zoghbi, H. Y. (1993) · Nature Genetics · doi:10.1038/ng0793-221 · Cited by 1,632 · cited 1× · see citing works
“previously described and characterized (1) and these mice have been backcrossed onto”
Self-citationSeverely increased risk of amyotrophic lateral sclerosis among Italian professional football players
Chio, A. (2005) · Brain · doi:10.1093/brain/awh373 · Cited by 484 · see citing works
Flagged first, then by citations
Research works printed but not linked: 13
- [2]Zoghbi HY Orr HT Pathogenic Mechanisms of a Polyglutamine-mediated Neurodegenerative Disease, Spinocerebellar Ataxia Type 1 Journal of Biological Chemistry 284 7425 7429 2009 18957430 PMC2658037
- [3]Cotman CW Berchtold NC Christie LA Exercise builds brain health: key roles of growth factor cascades and inflammation Trends Neurosci 30 464 472 2007 17765329
- [5]Mahoney DJ Rodriguez C Devries M Yasuda N Tarnopolsky MA Effects of high-intensity endurance exercise training in the G93A mouse model of amyotrophic lateral sclerosis Muscle & Nerve 29 656 662 2004 15116368
- [6]Watase K A long CAG repeat in the mouse Sca1 locus replicates SCA1 features and reveals the impact of protein solubility on selective neurodegeneration Neuron 34 905 919 2002 12086639
- [7]Astigarraga S A MAPK docking site is critical for downregulation of Capicua by Torso and EGFR RTK signaling EMBO J 26 668 677 2007 17255944 PMC1794389
- [8]Lam YC ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology Cell 127 1335 1347 2006 17190598
- [9]Crespo-Barreto J Fryer JD Shaw CA Orr HT Zoghbi HY Partial loss of ataxin-1 function contributes to transcriptional dysregulation in spinocerebellar ataxia type 1 pathogenesis PLoS Genet 6 e1001021 2010 20628574 PMC2900305
- [10]Kawamura-Saito M Fusion between CIC and DUX4 up-regulates PEA3 family genes in Ewing-like sarcomas with t(4;19)(q35;q13) translocation Hum Mol Genet 15 2125 2137 2006 16717057
- [11]Lim J Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1 Nature 452 713 718 2008 18337722 PMC2377396
- [12]Thomas PS Jr Loss of endogenous androgen receptor protein accelerates motor neuron degeneration and accentuates androgen insensitivity in a mouse model of X-linked spinal and bulbar muscular atrophy Hum Mol Genet 15 2225 2238 2006 16772330
- [13]Van Raamsdonk JM Loss of wild-type huntingtin influences motor dysfunction and survival in the YAC128 mouse model of Huntington disease Hum Mol Genet 14 1379 1392 2005 15829505
- [14]Vaz DV Treadmill training for ataxic patients: a single-subject experimental design Clin Rehabil 22 234 241 2008 18057087
- [15]Ilg W Intensive coordinative training improves motor performance in degenerative cerebellar disease Neurology 73 1823 1830 2009 19864636
Cited by
Sorted by citations
Mechanisms of protein toxicity in neurodegenerative diseases
Chung, C. G., Lee, H., & Lee, S. B. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2854-4 · Cited by 142 · see citing works
Polyglutamine Disease Toxicity Is Regulated by Nemo-like Kinase in Spinocerebellar Ataxia Type 1
Ju, H., Kokubu, H., Todd, T. W., Kahle, J. J., Kim, S., Richman, R., Chirala, K., Orr, H. T., Zoghbi, H. Y., & Lim, J. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.3465-12.2013 · Cited by 31 · see citing works
“Building on our studies of SCA1 and ATXN1, we found that neurodegeneration in SCA1 results from a gain of endogenous functions mediated by the polyglutamine-expanded mutant ATXN1, and from a concurrent partial loss of the beneficial functions of wild-type (WT) ATXN1 (Lim et al., 2008; CrespoBarreto et al., 2010; Fryer…”
BackgroundInfluentialSelf-citationZheng, F., Zhang, M., Ding, Q., Sethna, F., Yan, L., Moon, C., Yang, M., & Wang, H. (2016) · Learning & Memory · doi:10.1101/lm.040642.115 · Cited by 14 · see citing works
- Authors
- Fryer, J. D., Yu, P., Kang, H., Mandel-Brehm, C., Carter, A. N., Crespo-Barreto, J., Gao, Y., Flora, A., Shaw, C., Orr, H. T., & Zoghbi, H. Y.
- Affiliations
- Baylor College of Medicine (US)
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
- University of Minnesota (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Zoghbi, Huda Y.
- Venue
- Science
- Published
- 2011-11-04
- Volume
- 334
- Issue
- 6056
- Pages
- 690-693
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3232424
- OpenAlex
- W2075460872
- Cited by
- 162
- References
- 2
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 5 · 2023: 8 · 2022: 10 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 13 · 2017: 12 · 2016: 10 · 2015: 13 · 2014: 12 · 2013: 17 · 2012: 21
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5f32ns055545-03)
- National Institute of Neurological Disorders and Stroke (R37NS022920, NS 27699, NS 045667, T32NS043124, 1F32NS055545, NS022920, R01NS022920, F32 NS055545, R01NS045667, R37NS027699, NS27699-20S1, R01NS027699)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, P30HD024064)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- spinocerebellar ataxia type 1, physical activity, Capicua, ataxin-1, CAG repeat expansion, polyglutamine, epidermal growth factor, transcriptional repression, neurodegeneration, genetic rescue, disease survival, mouse model
- MeSH terms
- Ataxins, Ataxin-1, Animals, Cerebellum, Disease Models, Animal, Exercise Therapy, Mice, Inbred C57BL, Mice, Mutant Strains, Nerve Tissue Proteins, Nuclear Proteins, Repressor Proteins, Spinocerebellar Ataxias, Mice, Gene Knock-In Techniques
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