KEAP1-modifying small molecule reveals muted NRF2 signaling responses in neural stem cells from Huntington's disease patients
Open accessAbstract
Significance: Chronic neuroinflammation and oxidative stress are likely complicit in driving disease progression in Huntington's disease (HD). Here, we describe the mechanism of action of a unique chemical scaffold that is highly selective for activation of NRF2, the master transcriptional regulator of cellular antiinflammatory and antioxidant defense genes. The use of this scaffold revealed that NRF2 activation responses were muted in HD patient-derived neural stem cells, suggesting increased susceptibility of this critical renewable cell population to oxidative stress in HD brain. However, pharmacological activation of NRF2 was able to repress inflammatory responses in mouse microglia and astrocytes, the principal cellular mediators of neuroinflammation, and in blood monocytes from HD patients. Our results suggest multiple protective benefits of NRF2 activation for HD patients.
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Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
Li, Y., Jiang, Q. L., Cao, G.-F., Yao, J., & Yan, B. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373980 · Cited by 16,351 · see citing works
Guide for the Care and Use of Laboratory Animals: Eighth Edition
(2011) · doi:10.17226/12910 · Cited by 16,199 · see citing works
MACDONALD, M. (1993) · Cell · doi:10.1016/0092-8674(93)90585-e · Cited by 8,366 · see citing works
Eng, J. K., McCormack, A. L., & Yates, J. R. (1994) · Journal of the American Society for Mass Spectrometry · doi:10.1016/1044-0305(94)80016-2 · Cited by 6,484 · see citing works
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634 · see citing works
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630 · see citing works
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 · see citing works
Hornung, V., Bauernfeind, F., Halle, A., Samstad, E. O., Kono, H., Rock, K. L., Fitzgerald, K. A., & Latz, E. (2008) · Nature Immunology · doi:10.1038/ni.1631 · Cited by 3,065 · see citing works
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
Self-citationKobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224 · see citing works
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,158 · see citing works
Self-citationDinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947 · see citing works
Self-citationNrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
Kobayashi, E. H., Suzuki, T., Funayama, R., Nagashima, T., Hayashi, M., Sekine, H., Tanaka, N., Moriguchi, T., Motohashi, H., Nakayama, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms11624 · Cited by 1,878 · see citing works
Quantitative reactivity profiling predicts functional cysteines in proteomes
Weerapana, E., Wang, C., Simon, G. M., Richter, F., Khare, S., Dillon, M. B. D., Bachovchin, D. A., Mowen, K., Baker, D., & Cravatt, B. F. (2010) · Nature · doi:10.1038/nature09472 · Cited by 1,684 · see citing works
Self-citationZhang, Y., Talalay, P., Cho, C. G., & Posner, G. H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.6.2399 · Cited by 1,682 · see citing works
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480 · see citing works
Tabb, D. L., McDonald, W. H., & Yates, J. R. (2002) · Journal of Proteome Research · doi:10.1021/pr015504q · Cited by 1,369 · see citing works
Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex
Zhang, D. D., Lo, S., Cross, J. V., Templeton, D. J., & Hannink, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10941-10953.2004 · Cited by 1,262 · see citing works
Role of Pro-Inflammatory Cytokines Released from Microglia in Neurodegenerative Diseases
Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.10.004 · Cited by 1,165 · see citing works
Linker, R. A., Lee, D.-H., Ryan, S., van Dam, A. M., Conrad, R., Bista, P., Zeng, W., Hronowsky, X., Buko, A., Chollate, S., et al. (2011) · Brain · doi:10.1093/brain/awq386 · Cited by 1,155 · see citing works
McMahon, M., Itoh, K., Yamamoto, M., & Hayes, J. D. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300931200 · Cited by 1,141 · see citing works
Sirtuin 2 Inhibitors Rescue α-Synuclein-Mediated Toxicity in Models of Parkinson's Disease
Outeiro, T. F., Kontopoulos, E., Altmann, S. M., Kufareva, I., Strathearn, K. E., Amore, A. M., Volk, C. B., Maxwell, M. M., Rochet, J., McLean, P. J., et al. (2007) · Science · doi:10.1126/science.1143780 · Cited by 1,066 · see citing works
Self-citationThe cytoprotective role of the Keap1–Nrf2 pathway
Baird, L., & Dinkova‐Kostova, A. T. (2011) · Archives of Toxicology · doi:10.1007/s00204-011-0674-5 · Cited by 1,029 · see citing works
Self-citationWakabayashi, N., Dinkova-Kostova, A. T., Holtzclaw, W. D., Kang, M.-I., Kobayashi, A., Yamamoto, M., Kensler, T. W., & Talalay, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307301101 · Cited by 986 · see citing works
Cullinan, S. B., Gordan, J. D., Jin, J., Harper, J. W., & Diehl, J. A. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.19.8477-8486.2004 · Cited by 986 · see citing works
Neurogenesis in the striatum of the adult human brain
Ernst, A., Alkass, K., Bernard, S., Salehpour, M., Perl, S., Tisdale, J., Possnert, G., Druid, H., & Frisén, J. (2014) · Cell · doi:10.1016/j.cell.2014.01.044 · Cited by 937 · see citing works
Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation
Wakabayashi, N., Itoh, K., Wakabayashi, J., Motohashi, H., Noda, S., Takahashi, S., Imakado, S., KOTSUJI, T., Otsuka, F., Roop, D. R., et al. (2003) · Nature Genetics · doi:10.1038/ng1248 · Cited by 881 · see citing works
Selective striatal neuronal loss in a YAC128 mouse model of Huntington disease
Slow, E. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg169 · Cited by 799 · see citing works
Lee, J., Calkins, M. J., Chan, K., Kan, Y. W., & Johnson, J. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211558200 · Cited by 783 · see citing works
Does neuroinflammation fan the flame in neurodegenerative diseases?
Frank-Cannon, T. C., Alto, L. T., McAlpine, F. E., & Tansey, M. G. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-47 · Cited by 751 · see citing works
Björkqvist, M., Wild, E. J., Thiele, J., Silvestroni, A., André, R., Lahiri, N., Raibon, E., Lee, R. V., Benn, C., Soulet, D., et al. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080178 · Cited by 646 · see citing works
Self-citationEarly and Progressive Accumulation of Reactive Microglia in the Huntington Disease Brain
Sapp, E., Kegel, K. B., D, N. A. M., Hashikawa, T., Uchiyama, Y., Tohyama, K., Bhide, P. G., Vonsattel, J., & DiFiglia, M. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.2.161 · Cited by 537 · see citing works
Self-citationProchaska, H. J., & Santamaria, A. B. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90292-8 · Cited by 495 · see citing works
Mattis, V. B., Svendsen, S. P., Ebert, A., Svendsen, C., King, A. R., Casale, M., Winokur, S., Batugedara, G., Vawter, M., Donovan, P., et al. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.04.027 · Cited by 479 · see citing works
Self-citationThe Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation
Innamorato, N. G., Rojo, A. I., García‐Yagüe, Á. J., Yamamoto, M. P., CEBALLOS, M. L. D., & Cuadrado, A. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.1.680 · Cited by 479 · see citing works
The Nrf2 System as a Potential Target for the Development of Indirect Antioxidants
Jung, K.-A., & Kwak, M. (2010) · Molecules · doi:10.3390/molecules15107266 · Cited by 476 · see citing works
Two-site substrate recognition model for the Keap1-Nrf2 system: A hinge and latch mechanism
Tong, K. I., Kobayashi, A., Katsuoka, F., & Yamamoto, M. (2006) · Biological Chemistry · doi:10.1515/bc.2006.164 · Cited by 473 · see citing works
Microglial activation correlates with severity in Huntington disease: A clinical and PET study
Pavese, N., Gerhard, A., Tai, Y. F., Ho, A. K., Turkheimer, F., Barker, R. A., Brooks, D. J., & Piccini, P. (2006) · Neurology · doi:10.1212/01.wnl.0000222734.56412.17 · Cited by 462 · see citing works
Tong, K. I., Padmanabhan, B., Kobayashi, A., Shang, C., Hirotsu, Y., Yokoyama, S., & Yamamoto, M. P. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00753-07 · Cited by 447 · see citing works
McMahon, M. J., Lamont, D. J., Beattie, K. A., & Hayes, J. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007387107 · Cited by 445 · see citing works
Tsunemi, T., Ashe, T. D., Morrison, B. E., Epilepsia, K. S., Au, J., Vázquez‐Roque, R. A., Lazarowski, E. R., Damian, V. A., Masliah, E., & Spada, A. R. L. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003799 · Cited by 440 · see citing works
Inflammatory Process in Parkinsons Disease: Role for Cytokines
Nagatsu, T., & Sawada, M. (2005) · Current Pharmaceutical Design · doi:10.2174/1381612053381620 · Cited by 412 · see citing works
Baird, L., Llères, D., Swift, S., & Dinkova‐Kostova, A. T. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305687110 · Cited by 386 · see citing works
Self-citationGenetic Correction of Huntington’s Disease Phenotypes in Induced Pluripotent Stem Cells
An, M., Zhang, N.-Z., Scott, G., Montoro, D. T., Wittkop, T., Mooney, S., Melov, S., & Ellerby, L. (2012) · Cell Stem Cell · doi:10.1016/j.stem.2012.04.026 · Cited by 385 · see citing works
Self-citationActivation of NRF2 by Nitrosative Agents and H2O2 Involves KEAP1 Disulfide Formation
Fourquet, S., Guérois, R., Biard, D. S. F., & Tolédano, M. B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.051714 · Cited by 378 · see citing works
Rate of functional decline in Huntington’s disease
Marder, K., Zhao, H., Myers, R. H., Cudkowicz, M., Kayson, E., Kieburtz, K., Orme, C., Paulsen, J., Penney, J. B., Siemers, E., et al. (2000) · Neurology · doi:10.1212/wnl.54.2.452 · Cited by 362 · see citing works
Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors
Crotti, A., Benner, C., Kerman, B. E., Gosselin, D., Lagier-Tourenne, C., Zuccato, C., Cattaneo, E., Gage, F. H., Cleveland, D. W., & Glass, C. K. (2014) · Nature Neuroscience · doi:10.1038/nn.3668 · Cited by 333 · see citing works
Role of complement in neurodegeneration and neuroinflammation
Bonifati, D. M., & Kishore, U. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2006.03.007 · Cited by 310 · see citing works
Oxidative Damage in Huntington's Disease Pathogenesis
Browne, S. E., & Beal, M. F. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.2061 · Cited by 309 · see citing works
Proteomic and oxidative stress analysis in human brain samples of Huntington disease
Sorolla, M. A., Reverter‐Branchat, G., Tamarit, J., Ferrer, I., Ros, J., & Cabiscol, E. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.05.014 · Cited by 300 · see citing works
Validation of the multiple sensor mechanism of the Keap1-Nrf2 system
Takaya, K., Suzuki, T., Motohashi, H., Onodera, K., Satomi, S., Kensler, T. W., & Yamamoto, M. P. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.06.023 · Cited by 277 · see citing works
Weerapana, E., Speers, A. E., & Cravatt, B. F. (2007) · Nature Protocols · doi:10.1038/nprot.2007.194 · Cited by 276 · see citing works
Self-citationStructure of the BTB Domain of Keap1 and Its Interaction with the Triterpenoid Antagonist CDDO
Cleasby, A., Yon, J. R., Day, P. J., Richardson, C. J., Tickle, I. J., Williams, P. A., Callahan, J. F., Carr, R. A. E., Concha, N. O., Kerns, J. K., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098896 · Cited by 263 · see citing works
Neurodegeneration and Inflammation in Parkinson's disease
Phani, S., Loike, J. D., & Przedborski, S. (2012) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(11)70064-5 · Cited by 263 · see citing works
Nrf2 affects the efficiency of mitochondrial fatty acid oxidation
Ludtmann, M. H. R., Angelova, P. R., Zhang, Y., Abramov, A. Y., & Dinkova‐Kostova, A. T. (2013) · Biochemical Journal · doi:10.1042/bj20130863 · Cited by 241 · see citing works
Self-citationDalrymple, A., Wild, E. J., Joubert, R., Sathasivam, K., Björkqvist, M., Petersén, Å., Jackson, G. S., Isaacs, J. D., Kristiansen, M., Bates, G. P., et al. (2007) · Journal of Proteome Research · doi:10.1021/pr0700753 · Cited by 223 · see citing works
Self-citationThe Sirtuin 2 Inhibitor AK-7 Is Neuroprotective in Huntington’s Disease Mouse Models
Chopra, V., Quinti, L., Kim, J., Vollor, L., Narayanan, K. L., Edgerly, C. K., Cipicchio, P. M., Lauver, M. A., Choi, S. H., Silverman, R. B., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.11.001 · Cited by 214 · see citing works
Self-citationPolitis, M., Pavese, N., Tai, Y. F., Kiferle, L., Mason, S. L., Brooks, D. J., Tabrizi, S. J., Barker, R. A., & Piccini, P. (2011) · Human Brain Mapping · doi:10.1002/hbm.21008 · Cited by 212 · see citing works
Self-citationAn Auto-regulatory Loop between Stress Sensors INrf2 and Nrf2 Controls Their Cellular Abundance
Lee, O.-H., Jain, A. K., Papusha, V. Z., & Jaiswal, A. K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706517200 · Cited by 205 · see citing works
Distinct neuroinflammatory profile in post-mortem human Huntington's disease
Silvestroni, A., Faull, R. L. M., Strand, A. D., & Möller, T. (2009) · Neuroreport · doi:10.1097/wnr.0b013e32832e34ee · Cited by 204 · see citing works
Quantitative analysis of chromatin compaction in living cells using FLIM–FRET
Llères, D., James, J. L., Swift, S., Norman, D., & Lamond, A. I. (2009) · The Journal of Cell Biology · doi:10.1083/jcb.200907029 · Cited by 176 · see citing works
Self-citationNeuroinflammation in Huntington’s disease
Möller, T. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0430-7 · Cited by 174 · see citing works
Kaidery, N. A., Banerjee, R., Yang, L., Smirnova, N. A., Hushpulian, D. M., Liby, K. T., Williams, C. R., Yamamoto, M. P., Kensler, T. W., Ratan, R. R., et al. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4491 · Cited by 172 · see citing works
Stack, C., Ho, D. J., Wille, E. J., Calingasan, N. Y., Williams, C. R., Liby, K. T., Sporn, M. B., Dumont, M., & Beal, M. F. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.03.017 · Cited by 171 · see citing works
Monitoring Keap1–Nrf2 interactions in single live cells
Baird, L., Swift, S., Llères, D., & Dinkova‐Kostova, A. T. (2014) · Biotechnology Advances · doi:10.1016/j.biotechadv.2014.03.004 · Cited by 171 · see citing works
Self-citationEvidence of Oxidant Damage in Huntington's Disease: Translational Strategies Using Antioxidants
Stack, E. C., Matson, W. R., & Ferrante, R. J. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.008 · Cited by 167 · see citing works
Lee, D.-H., Gold, R., & Linker, R. A. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms130911783 · Cited by 161 · see citing works
Fractalkine activates NRF2/NFE2L2 and heme oxygenase 1 to restrain tauopathy-induced microgliosis
Lastres-Becker, I., Innamorato, N. G., Jaworski, T., Rábano, A., Kügler, S., Van Leuven, F., & Cuadrado, A. (2014) · Brain · doi:10.1093/brain/awt323 · Cited by 160 · see citing works
Li, X., Valencia, A., Sapp, E., Masso, N., Alexander, J. S., Reeves, P., Kegel, K. B., D, N. A. M., & DiFiglia, M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.5865-09.2010 · Cited by 159 · see citing works
Self-citationA tale on animal models of Parkinson's disease
Bézard, E., & Przedborski, S. (2011) · Movement Disorders · doi:10.1002/mds.23696 · Cited by 158 · see citing works
Antioxidants in Huntington's disease
Johri, A., & Beal, M. F. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.11.014 · Cited by 158 · see citing works
The “Prochaska” Microtiter Plate Bioassay for Inducers of NQO1
Fahey, J. W., Dinkova‐Kostova, A. T., Stephenson, K. K., & Talalay, P. (2004) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(04)82014-7 · Cited by 157 · see citing works
Self-citationEfficacy of Fumaric Acid Esters in the R6/2 and YAC128 Models of Huntington's Disease
Ellrichmann, G., Petrasch‐Parwez, E., Lee, D.-H., Reick, C., Arning, L., Carsten Saft, C., Gold, R., & Linker, R. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016172 · Cited by 155 · see citing works
Xu, K., Xu, Y., Brown-Jermyn, D., Chen, J., Ascherio, A., Dluzen, D. E., & Schwarzschild, M. A. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3008-05.2006 · Cited by 142 · see citing works
Self-citationChen, X., Wales, P., Quinti, L., Zuo, F., Moniot, S., Hérisson, F., Rauf, N. A., Wang, H., Silverman, R. B., Ayata, C., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0116919 · Cited by 138 · see citing works
Self-citationImaging microglial activation in Huntington's disease
Tai, Y., Pavese, N., Gerhard, A., Tabrizi, S. J., Barker, R. A., Brooks, D. J., & Piccini, P. P. (2006) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2006.10.029 · Cited by 137 · see citing works
Self-citationBG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety
Fox, R. J., Kita, M., Cohan, S. L., Henson, L. J., Zambrano, J., Scannevin, R. H., O'Gorman, J., Novas, M., Dawson, K. T., & Phillips, J. T. (2014) · Current Medical Research and Opinion · doi:10.1185/03007995.2013.849236 · Cited by 124 · see citing works
Bertrand, H. C., Schaap, M., Baird, L., Georgakopoulos, N., Fowkes, A., Thiollier, C., Kaatchi, H., Dinkova‐Kostova, A. T., & Wells, G. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b00602 · Cited by 123 · see citing works
Self-citationDisrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration
Chen, X. M., Burdett, T. C., Desjardins, C. A., Logan, R. A., Cipriani, S., Xu, Y., & Schwarzschild, M. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1217296110 · Cited by 123 · see citing works
Self-citationLiu, H., Dinkova‐Kostova, A. T., & Talalay, P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808346105 · Cited by 121 · see citing works
Self-citationNrf2 Activation Protects against Solar-Simulated Ultraviolet Radiation in Mice and Humans
Knatko, E. V., Ibbotson, S. H., Zhang, Y., Higgins, M., Fahey, J. W., Talalay, P., Dawe, R. S., Ferguson, J., Huang, J. T.-J., Clarke, R. G., et al. (2015) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-14-0362 · Cited by 121 · see citing works
Self-citationAbnormal peripheral chemokine profile in Huntington’s disease
Wild, E. J., Magnusson, A., Lahiri, N., Krus, U., Orth, M., Tabrizi, S. J., & Björkqvist, M. (2011) · PLoS Currents · doi:10.1371/currents.rrn1231 · Cited by 119 · see citing works
Self-citationWilliamson, T. P., Johnson, D. A., & Johnson, J. A. (2012) · NeuroToxicology · doi:10.1016/j.neuro.2012.01.015 · Cited by 118 · see citing works
Neuroinflamm-Aging and Neurodegenerative Diseases: An Overview
Pizza, V., Agresta, A., D’Acunto, C. W., Festa, M., & Capasso, A. (2011) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152711796235014 · Cited by 117 · see citing works
Jin, Y. N., Yu, Y. V., Gundemir, S., Jo, C., Cui, M., Tieu, K., & Johnson, G. V. W. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057932 · Cited by 102 · see citing works
Polucci, P., Magnaghi, P., Angiolini, M., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3013213 · Cited by 92 · see citing works
Quinti, L., Casale, M., Moniot, S., Pais, T. F., Kanegan, M. J. V., Kaltenbach, L. S., Pallos, J., Lim, R. G., Naidu, S. D., Runne, H., et al. (2016) · Cell chemical biology · doi:10.1016/j.chembiol.2016.05.015 · Cited by 89 · see citing works
Self-citationA Small-Molecule Inducer of the Antioxidant Response Element
Hur, W., Sun, Z., Jiang, T., Mason, D. E., Peters, E. C., Zhang, D. D., Luesch, H., Schultz, P. G., & Gray, N. S. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2010.03.013 · Cited by 81 · see citing works
Eggler, A. L., Luo, Y., van Breemen, R. B., & Mesecar, A. D. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700217c · Cited by 80 · see citing works
ST14A Cells Have Properties of a Medium-Size Spiny Neuron
Ehrlich, M. E., Conti, L., Toselli, M., Taglietti, L., Fiorillo, E., Taglietti, V., Ivković, S., Guinea, B., Tranberg, A., Sipione, S., et al. (2001) · Experimental Neurology · doi:10.1006/exnr.2000.7551 · Cited by 77 · see citing works
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- Authors
- Quinti, L., Dayalan Naidu, S., Träger, U., Chen, X., Kegel-Gleason, K., Llères, D., Connolly, C., Chopra, V., Low, C., Moniot, S., Sapp, E., Tousley, A. R., Vodicka, P., Van Kanegan, M. J., Kaltenbach, L. S., Crawford, L. A., Fuszard, M., Higgins, M., Miller, J. R. C., Farmer, R. E., Potluri, V., Samajdar, S., Meisel, L., Zhang, N., Snyder, A., Stein, R., Hersch, S. M., Ellerby, L. M., Weerapana, E., Schwarzschild, M. A., Steegborn, C., Leavitt, B. R., Degterev, A., Tabrizi, S. J., Lo, D. C., DiFiglia, M., Thompson, L. M., Dinkova-Kostova, A. T., & Kazantsev, A. G.
- Affiliations
- Harvard University (US)
- Division of Cancer Research, School of Medicine, University of Dundee, Dundee DD1 9SY, Scotland, United Kingdom;
- UCL Queen Square Institute of Neurology (GB)
- Institut de Génétique Moléculaire de Montpellier (FR)
- University of British Columbia (CA)
- Tufts University (US)
- University of Bayreuth (DE)
- Department of Neurology, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114;
- Center for Drug Discovery, Duke University Medical Center, Durham, NC 27710;
- Duke Medical Center (US)
- Boston College (US)
- University of Dundee (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Aurigene Discovery Technologies (India) (IN)
- Buck Institute for Research on Aging (US)
- Targanox, Cambridge Research Laboratories, Cambridge, MA 02139;
- University of California, Irvine (US)
- ORCID
- Träger, Ulrike
- Kegel-Gleason, Kimberly
- Llères, David
- Moniot, Sébastien
- Sapp, Ellen
- Tousley, Adelaide R.
- Crawford, Lisa A.
- Higgins, Maureen
- Miller, James R. C.
- Farmer, Ruth E.
- Samajdar, Susanta
- Zhang, Ningzhe
- Snyder, Andrew
- Stein, Ross
- Hersch, Steven M.
- Ellerby, Lisa M.
- Weerapana, Eranthie
- Schwarzschild, Michael A.
- Steegborn, Clemens
- Leavitt, Blair R.
- Degterev, Alexei
- Tabrizi, Sarah J.
- Lo, Donald C.
- DiFiglia, Marian
- Thompson, Leslie M.
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-05-22
- Volume
- 114
- Issue
- 23
- Pages
- E4676-E4685
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5468652
- OpenAlex
- W2618292058
- Cited by
- 140
- References
- 101
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 16 · 2023: 18 · 2022: 25 · 2021: 13 · 2020: 24 · 2019: 9 · 2018: 7 · 2017: 5
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion, other-oa)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- UCL Discovery (University College London) (submittedVersion)
- ERef Bayreuth (University of Bayreuth) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- CHDI Foundation
- Alzheimer Forschung Initiative (14834)
- Wellcome Trust (200181/Z/15/Z)
- Cancer Research UK (C20953 / A18644, A18644, BB/J007498/1, C20953, 18644)
- Rosetrees Trust
- National Institutes of Health
- Directorate for Biological Sciences
- Medical Research Council (MR/L02053X/1)
- Biotechnology and Biological Sciences Research Council (BB/L01923X/1, BB/J007498/1)
- National Institute of General Medical Sciences (GM080356, R01GM118431, R01GM080356)
- National Institute of Neurological Disorders and Stroke (U01NS066912, NS100529, R01NS100529)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Keywords
- Keap1, Nrf2 signaling, Huntington's disease, small molecule inducers, E3 ubiquitin ligase, neural stem cells, microglia, astrocytes, monocytes, inflammatory cytokines, interleukin-6, neuroinflammation, antioxidant response
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Adult, Aged, Animals, Brain, Cells, Cultured, Disease Models, Animal, Female, Humans, Huntington Disease, Macrophages, Male, Mice, Inbred C57BL, Middle Aged, Protein Conformation, Signal Transduction, Cytokines, Microglia, Neuroprotective Agents, MPTP Poisoning, NF-E2-Related Factor 2, Mice, Rats, HEK293 Cells, Neural Stem Cells
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.
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