Cited by 2,347Genetic Neurodegenerative DiseasesAutophagy in Disease and TherapyGenetics and Neurodevelopmental Disorders

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Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

Ravikumar, Brinda, Vacher, Coralie, Berger, Zdenek, Davies, Janet E, Luo, Shouqing, Oroz, Lourdes G, Scaravilli, Francesco, Easton, Douglas F, Duden, Rainer, O'Kane, Cahir J, Rubinsztein, David C·2004·Nature Genetics

DOI 10.1038/ng1362

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Abstract

Huntington disease is one of nine inherited neurodegenerative disorders caused by a polyglutamine tract expansion. Expanded polyglutamine proteins accumulate abnormally in intracellular aggregates. Here we show that mammalian target of rapamycin (mTOR) is sequestered in polyglutamine aggregates in cell models, transgenic mice and human brains. Sequestration of mTOR impairs its kinase activity and induces autophagy, a key clearance pathway for mutant huntingtin fragments. This protects against polyglutamine toxicity, as the specific mTOR inhibitor rapamycin attenuates huntingtin accumulation and cell death in cell models of Huntington disease, and inhibition of autophagy has the converse effects. Furthermore, rapamycin protects against neurodegeneration in a fly model of Huntington disease, and the rapamycin analog CCI-779 improved performance on four different behavioral tasks and decreased aggregate formation in a mouse model of Huntington disease. Our data provide proof-of-principle for the potential of inducing autophagy to treat Huntington disease.

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LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
Kabeya, Y., Mizushima, N., Ueno, T., Yamamoto, A., Kirisako, T., Noda, T., Kominami, E., Ohsumi, Y., & Yoshimori, T. (2000) · The EMBO Journal · doi:10.1093/emboj/19.21.5720 · Cited by 6,605
Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice
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
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
TOR, a Central Controller of Cell Growth
Schmelzle, T., & Hall, M. N. (2000) · Cell · doi:10.1016/s0092-8674(00)00117-3 · Cited by 1,914
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
α-Synuclein Is Degraded by Both Autophagy and the Proteasome
Webb, J. L., Ravikumar, B., Atkins, J., Skepper, J. N., & Rubinsztein, D. C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300227200 · Cited by 1,429
Self-citation
Histone deacetylase inhibitors arrest polyglutamine-dependent neurodegeneration in Drosophila
Steffan, J. S., Bodai, L., Pallos, J., Poelman, M., McCampbell, A., Apostol, B. L., Kazantsev, A., Schmidt, E., Zhu, Y.-Z., Greenwald, M., et al. (2001) · Nature · doi:10.1038/35099568 · Cited by 1,228
Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy
Ravikumar, B. (2002) · Human Molecular Genetics · doi:10.1093/hmg/11.9.1107 · Cited by 1,099
Self-citation
Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E
Fingar, D. C., Salama, S., Tsou, C., Harlow, E., & Blenis, J. (2002) · Genes & Development · doi:10.1101/gad.995802 · Cited by 1,093
GβL, a Positive Regulator of the Rapamycin-Sensitive Pathway Required for the Nutrient-Sensitive Interaction between Raptor and mTOR
Kim, D., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00114-x · Cited by 992

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Kirk, J. A., Cheung, J. Y., & Feldman, A. M. (2021) · Journal of Clinical Investigation · doi:10.1172/jci149415 · Cited by 76
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Li, X., Liu, H., Fischhaber, P. L., & Tang, T.-S. (2015) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.06.004 · Cited by 78
Alteration of protein folding and degradation in motor neuron diseases: Implications and protective functions of small heat shock proteins
Carra, S., Crippa, V., Rusmini, P., Boncoraglio, A., Minoia, M., Giorgetti, E., Kampinga, H. H., & Poletti, A. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.09.009 · Cited by 77
The PI 3-kinase regulator Vps15 is required for autophagic clearance of protein aggregates
Lindmo, K., Brech, A., Finley, K. D., Gaumer, S., Contamine, D., Rusten, T. E., & Stenmark, H. (2008) · Autophagy · doi:10.4161/auto.5829 · Cited by 76
Interplay Between HDAC6 and Its Interacting Partners: Essential Roles in the Aggresome-Autophagy Pathway and Neurodegenerative Diseases
Yan, J. (2014) · DNA and Cell Biology · doi:10.1089/dna.2013.2300 · Cited by 77
Age-related changes in the function of autophagy in rat kidneys
Cui, J., Bai, X.-Y., Shi, S., Cui, S., Hong, Q., Cai, G., & Chen, X. (2012) · AGE · doi:10.1007/s11357-011-9237-1 · Cited by 75
Complex neuroprotective and neurotoxic effects of histone deacetylases
Thomas, E. A., & D’Mello, S. R. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14309 · Cited by 76
Geniposide-mediated protection against amyloid deposition and behavioral impairment correlates with downregulation of mTOR signaling and enhanced autophagy in a mouse model of Alzheimer's disease
Zhang, Z., Wang, X., Zhang, D., Liu, Y., & Lin, L. (2019) · Aging · doi:10.18632/aging.101759 · Cited by 76
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Pallàs, M., Porquet, D., Vicente, A., & Sanfeliu, C. (2013) · Current Pharmaceutical Design · doi:10.2174/1381612811319380005 · Cited by 75
S100A8 Contributes to Drug Resistance by Promoting Autophagy in Leukemia Cells
Yang, M., Pei, Z., Kang, R., Yan, Y., Yang, L., Tang, D., & Cao, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0097242 · Cited by 76
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Accelerating the clearance of mutant huntingtin protein aggregates through autophagy induction by europium hydroxide nanorods
Wei, P., Zhang, L., Nethi, S. K., Barui, A. K., Lin, J., Zhou, W., Shen, Y., Man, N., Zhang, Y., Xu, J., et al. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.10.024 · Cited by 75
Molecular Pathogenesis in Huntington’s Disease
Illarioshkin, S. N., Klyushnikov, S. A., Vigont, V. A., Seliverstov, Y. A., & Kaznacheyeva, E. V. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918090043 · Cited by 79
Autophagy activation and neuroprotection by progesterone in the G93A-SOD1 transgenic mouse model of amyotrophic lateral sclerosis
Kim, J., Kim, T.-Y., Cho, K.-S., Kim, H., & Koh, J. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.07.011 · Cited by 74
A Picky Eater: Exploring the Mechanisms of Selective Autophagy in Human Pathologies
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Succinic semialdehyde dehydrogenase deficiency (SSADHD): Pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism
Malaspina, P., Roullet, J., Pearl, P. L., Ainslie, G. R., Vogel, K. R., & Gibson, K. M. (2016) · Neurochemistry International · doi:10.1016/j.neuint.2016.06.009 · Cited by 73
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Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS
Chang, C.-F., Lee, Y., Lee, K., Lin, H., Chen, C., Shen, C.-K. J., & Huang, C.-C. S. (2016) · Journal of Biomedical Science · doi:10.1186/s12929-016-0290-z · Cited by 74
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Lakhani, R., Vogel, K. R., Till, A., Liu, J., Burnett, S. F., Gibson, K. M., & Subramani, S. (2014) · EMBO Molecular Medicine · doi:10.1002/emmm.201303356 · Cited by 75
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Shannon, K. M., & Fraint, A. (2015) · Movement Disorders · doi:10.1002/mds.26331 · Cited by 72
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Maiuri, M. C., Grassia, G., Platt, A. M., Carnuccio, R., Ialenti, A., & Maffia, P. (2013) · Mediators of Inflammation · doi:10.1155/2013/584715 · Cited by 72
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Membrane trafficking in neuronal maintenance and degeneration
Wang, D., Chan, C., Cherry, S., & Hiesinger, P. R. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1201-4 · Cited by 74
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Maruzs, T., Simon‐Vecsei, Z., Kiss, V., Csizmadia, T., & Juhász, G. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00140 · Cited by 75
Huntingtin inclusion bodies are iron‐dependent centers of oxidative events
Firdaus, W. J. J., Wyttenbach, A., Giuliano, P., Kretz‐Remy, C., Currie, R. W., & Arrigo, A. (2006) · The FEBS Journal · doi:10.1111/j.1742-4658.2006.05537.x · Cited by 71
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Kim, Y., Choi, H., Lee, W., Park, H., Kam, T.-I., Hong, S.-H., Nah, J., Jung, S., Shin, B., Lee, H., et al. (2016) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.12.006 · Cited by 71
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The immunopathogenic role of reactive oxygen species in Alzheimer disease.
Mohsenzadegan, M., & Mirshafiey, A. (2012) · PubMed · Cited by 71
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Tateda, S., Kanno, H., Ozawa, H., Sekiguchi, A., Yahata, K., Yamaya, S., & Itoi, E. (2016) · Journal of Orthopaedic Research® · doi:10.1002/jor.23328 · Cited by 71
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Wu, A., Wu, J., Wong, V. K. W., Zhu, Y. Z., Lo, A., Liu, L., & Law, B. Y. K. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.11.002 · Cited by 71
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Huang, C., Yan, S., & Zhang, Z. (2020) · Translational Neurodegeneration · doi:10.1186/s40035-020-00219-w · Cited by 75
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Ohne, Y., Takahara, T., Hatakeyama, R., Matsuzaki, T., Noda, M., Mizushima, N., & Maeda, T. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m801546200 · Cited by 70
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Berger, Z., Ttofi, E. K., Michel, C. H., Pasco, M. Y., Tenant, S., Rubinsztein, D. C., & O’Kane, C. J. (2005) · Human Molecular Genetics · doi:10.1093/hmg/ddi331 · Cited by 70
Self-citation
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Fujita, K., Nakamura, Y., Oka, T., Ito, H., Tamura, T., Tagawa, K., Sasabe, T., Katsuta, A., Motoki, K., Shiwaku, H., et al. (2013) · Nature Communications · doi:10.1038/ncomms2828 · Cited by 70
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Otsubo, Y., Nakashima, A., Yamamoto, M. P., & Yamashita, A. (2017) · Biomolecules · doi:10.3390/biom7030050 · Cited by 69
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Richard, P., Feng, S., Tsai, Y.-L., Li, W., Rinchetti, P., Muhith, U., Irizarry-Cole, J., Stolz, K., Sanz, L. A., Hartono, S. R., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1796292 · Cited by 71
Protein homeostasis and aging: Role of ubiquitin protein ligases
Jana, N. R. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.02.009 · Cited by 67
Genetic Modifiers of the Drosophila Blue Cheese Gene Link Defects in Lysosomal Transport With Decreased Life Span and Altered Ubiquitinated-Protein Profiles
Simonsen, A., Cumming, R. C., Lindmo, K., Galaviz, V., Cheng, S., Rusten, T. E., & Finley, K. D. (2007) · Genetics · doi:10.1534/genetics.106.065011 · Cited by 67
Palmitate induces endoplasmic reticulum stress and autophagy in mature adipocytes: Implications for apoptosis and inflammation
Yin, J.-J., Wang, Y., Gu, L., Fan, N., Ma, Y., & Peng, Y. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2085 · Cited by 67
Carbamazepine as a Novel Small Molecule Corrector of Trafficking-impaired ATP-sensitive Potassium Channels Identified in Congenital Hyperinsulinism
Chen, P., Olson, E. M., Zhou, Q., Kryukova, Y. N., Sampson, H. M., Thomas, D. Y., & Shyng, S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.470948 · Cited by 67
Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein
Al‐Ramahi, I., Giridharan, S. S. P., Chen, Y., Patnaik, S., Safren, N., Hasegawa, J., de Haro, M., Gee, A. K. W., Titus, S. A., Jeong, H., et al. (2017) · eLife · doi:10.7554/elife.29123 · Cited by 70
The Role of VPS35 in the Pathobiology of Parkinson’s Disease
Sassone, J., Reale, C., Dati, G., Regoni, M., Pellecchia, M. T., & Garavaglia, B. (2020) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-020-00849-8 · Cited by 72
The Emerging Roles of Autophagy in Human Diseases
Lei, Y., & Klionsky, D. J. (2021) · Biomedicines · doi:10.3390/biomedicines9111651 · Cited by 68
Autophagy Modulation for Alzheimer’s Disease Therapy
Zhu, X., Yu, J., Jiang, T., & Tan, L. (2013) · Molecular Neurobiology · doi:10.1007/s12035-013-8457-z · Cited by 66
l-Glutamine deprivation induces autophagy and alters the mTOR and MAPK signaling pathways in porcine intestinal epithelial cells
Zhu, Y., Lin, G., Dai, Z., Zhou, T., Li, T., Yuan, T., Wu, Z., Wu, G., & Wang, J. (2014) · Amino Acids · doi:10.1007/s00726-014-1785-0 · Cited by 67
Autophagy and cell reprogramming
Wang, S., Xia, P., Rehm, M., & Fan, Z. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1829-3 · Cited by 66
Huntingtin’s Function in Axonal Transport Is Conserved in Drosophila melanogaster
Zala, D., Hinckelmann, M.-V., & Saudou, F. (2013) · PLoS ONE · doi:10.1371/journal.pone.0060162 · Cited by 66
Autophagy in Dementias
Kragh, C. L., Ubhi, K. K., Wyss‐Coray, T., & Masliah, E. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00545.x · Cited by 66
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Wang, S., Li, B., Qiao, H., Lv, X., Liang, Q., Shi, Z., Xia, W., Ji, F., & Jiao, J. (2014) · EMBO Reports · doi:10.15252/embr.201338343 · Cited by 67
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Xiao, L., Zhou, Y., Zhu, L., Yang, S., Huang, R. S., Shi, W., Peng, B., & Xiao, Y. (2018) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.3396 · Cited by 66
Impact of ER Stress and ER-Mitochondrial Crosstalk in Huntington’s Disease
Maity, S., Komal, P., Kumar, V., Saxena, A., Tungekar, A., & Chandrasekar, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020780 · Cited by 64
Impaired autophagy and delayed autophagic clearance of transforming growth factor β-induced protein (TGFBI) in granular corneal dystrophy type 2
Choi, S., Kim, B.-Y., Dadakhujaev, S., Oh, J.-Y., Kim, T., Kim, J. Y., & Kim, E. K. (2012) · Autophagy · doi:10.4161/auto.22067 · Cited by 65
The role of autophagy in endoplasmic reticulum stress-induced pancreatic β cell death
Yin, J.-J., Li, Y., Wang, Y., Liu, G., Wang, J., Zhu, X.-O., & Pan, S. (2012) · Autophagy · doi:10.4161/auto.8.2.18807 · Cited by 65
Short-Term Treatment With Rapamycin and Dietary Restriction Have Overlapping and Distinctive Effects in Young Mice
Fok, W. C., Zhang, Y., Salmon, A. B., Bhattacharya, A., Gunda, R., Jones, D. P., Ward, W. F., Fisher, K., Richardson, A. G., & Pérez, V. (2012) · The Journals of Gerontology Series A · doi:10.1093/gerona/gls127 · Cited by 66
mTOR dysfunction contributes to vacuolar pathology and weakness in valosin-containing protein associated inclusion body myopathy
Ching, J. K., Elizabeth, S., Ju, J.-S., Lusk, C., Pittman, S. K., & Weihl, C. C. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds524 · Cited by 65
Autophagy in aging and in neurodegenerative disorders
Rajawat, Y. S., & Bossis, I. (2008) · HORMONES · doi:10.14310/horm.2002.1111037 · Cited by 66
Rapamycin alleviates pathogenesis of a new Drosophila model of ALS-TDP
Cheng, C., Lin, M.-J., & Shen, C.-K. J. (2015) · Journal of Neurogenetics · doi:10.3109/01677063.2015.1077832 · Cited by 66
Rosiglitazone protects against palmitate-induced pancreatic beta-cell death by activation of autophagy via 5′-AMP-activated protein kinase modulation
Wu, J., Wu, J.-J., Yang, L., Wei, L., & Zou, D. (2012) · Endocrine · doi:10.1007/s12020-012-9826-5 · Cited by 65
MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells
Chen, K., Fan, W., Wang, X., Xiao, K., Wu, G., & Hu, C. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.09.026 · Cited by 64
Therapeutic induction of autophagy to modulate neurodegenerative disease progression
Hochfeld, W. E., Lee, S. H. F., & Rubinsztein, D. C. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2012.189 · Cited by 66
Self-citation
Proteasome Inhibitors Activate Autophagy Involving Inhibition of PI3K-Akt-mTOR Pathway as an Anti-Oxidation Defense in Human RPE Cells
Tang, B., Cai, J., Sun, L. N., Li, Y., Qu, J., Snider, B. J., & Wu, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103364 · Cited by 64

Authors: Ravikumar, B., Vacher, C., Berger, Z., Davies, J. E., Luo, S., Oroz, L. G., Scaravilli, F., Easton, D. F., Duden, R., O'Kane, C. J., & Rubinsztein, D. C.
Affiliations: University of Cambridge (GB)
UCL Queen Square Institute of Neurology (GB)
Addenbrooke's Hospital (GB)
Corresponding author: Rubinsztein, David C
ORCID: Berger, Zdenek
Davies, Janet E
Luo, Shouqing
Easton, Douglas F
Duden, Rainer
Rubinsztein, David C
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2004-05-16
Volume: 36
Issue: 6
Pages: 585-595
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng1362
OpenAlex: W2111567059
Cited by: 2,347
References: 49
Citations by year: 2026: 39 · 2025: 43 · 2024: 56 · 2023: 61 · 2022: 94 · 2021: 113 · 2020: 101 · 2019: 110 · 2018: 114 · 2017: 94 · 2016: 126 · 2015: 145 · 2014: 148 · 2013: 153 · 2012: 159
FWCI: 29.14
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: Wellcome Trust
Commonwealth Scholarship Commission
Cambridge Overseas Trust
Directorate for Biological Sciences
Medical Research Council
Biotechnology and Biological Sciences Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
Keywords: Huntington's disease, mTOR, autophagy, polyglutamine expansion, rapamycin, temsirolimus, mutant huntingtin, protein aggregation, neurodegeneration, kinase inhibition, therapeutic target
MeSH terms: Huntingtin Protein, Animals, Autophagy, Disease Models, Animal, Drosophila melanogaster, Female, Humans, Huntington Disease, Male, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Nuclear Proteins, Peptides, Protein Kinases, Protein Biosynthesis, COS Cells, Sirolimus, Macromolecular Substances, Protein Kinase Inhibitors, Mice, TOR Serine-Threonine Kinases

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Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

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