Inhibition of p70 S6 kinase activity by A77 1726 induces autophagy and enhances the degradation of superoxide dismutase 1 (SOD1) protein aggregates
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Autophagy plays a central role in degrading misfolded proteins such as mutated superoxide dismutase 1 (SOD1), which forms aggregates in motor neurons and is involved in the pathogenesis of amyotrophic lateral sclerosis (ALS). Autophagy is activated when UNC-51-like kinase 1 (ULK1) is phosphorylated at S555 and activated by AMP-activated protein kinase (AMPK). Autophagy is suppressed when ULK1 is phosphorylated at S757 by the mechanistic target of rapamycin (mTOR). Whether p70 S6 kinase 1 (S6K1), a serine/threonine kinase downstream of mTOR, can also regulate autophagy remains uncertain. Here we report that inhibition of S6K1 by A77 1726, the active metabolite of an anti-inflammatory drug leflunomide, induced mTOR feedback activation and ULK1 S757 phosphorylation in NSC34 cells, a hybrid mouse motoneuron cell line. Unexpectedly, A77 1726 did not suppress but rather induced autophagy by increasing AMPK T172 and ULK1 S555 phosphorylation. Similar observations were made with PF-4708671, a specific S6K1 inhibitor, or with S6K1 siRNA. Further studies showed that A77 1726 induced AMPK phosphorylation by activating the TGF-β-activated kinase 1 (TAK1). Functional studies revealed that A77 1726 induced co-localization of mutant SOD1 G93A protein aggregates with autophagosomes and accelerated SOD1 G93A protein degradation, which was blocked by inhibition of autophagy through autophagy-related protein 7 (ATG7) siRNA. Our study suggests that S6K1 inhibition induces autophagy through TAK1-mediated AMPK activation in NSC34 cells, and that blocking S6K1 activity by a small molecule inhibitor such as leflunomide may offer a new strategy for ALS treatment.
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In G93A mice, dysregulation of autophagy leads to the elimination of misfolded proteins such as superoxide dismutase 1, and this dismutant form accumulates in the motor neurons involved in the pathogenesis of ALS.
“Dysregulation of autophagy appears to lead to the elimination of misfolded proteins, such as superoxide dismutase 1, in G93A mice, and this dismutant form accumulates in the motor neurons involved in the pathogenesis of ALS (88).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [88]
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Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894 · see citing works
Phosphorylation of ULK1 (hATG1) by AMP-Activated Protein Kinase Connects Energy Sensing to Mitophagy
Egan, D. F., Shackelford, D. B., Mihaylova, M. M., Gelino, S., Kohnz, R. A., Mair, W., Vasquez, D. S., Joshi, A., Gwinn, D. M., Taylor, R., et al. (2011) · Science · doi:10.1126/science.1196371 · Cited by 2,600 · see citing works
Amyotrophic Lateral Ssclerosis and Structural Defects in Cu,Zn Superoxide Dismutase
Deng, H., Hentati, A., Tainer, J. A., Iqbal, Z., Cayabyab, A., Hung, W.-Y., Getzoff, E. D., Hu, P., Herzfeldt, B., Roos, R. P., et al. (1993) · Science · doi:10.1126/science.8351519 · Cited by 1,479 · see citing works
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120 · see citing works
Metabolic control of autophagy
Galluzzi, L., Pietrocola, F., Levine, B., & Kroemer, G. (2014) · Cell · doi:10.1016/j.cell.2014.11.006 · Cited by 855 · see citing works
Autophagy regulation by nutrient signaling
Russell, R. C., Yuan, H., & Guan, K. (2013) · Cell Research · doi:10.1038/cr.2013.166 · Cited by 713 · see citing works
The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR
Egan, D., Kim, J., Shaw, R. J., & Guan, K.-L. (2011) · Autophagy · doi:10.4161/auto.7.6.15123 · Cited by 627 · see citing works
Lithium delays progression of amyotrophic lateral sclerosis
Fornai, F., Longone, P., Cafaro, L., Kastsiuchenka, O., Ferrucci, M., Manca, M. L., Lazzeri, G., Spalloni, A., Bellio, N., Lenzi, P., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708022105 · Cited by 550 · see citing works
Ubiquitin-mediated activation of TAK1 and IKK
Adhikari, A., Xu, M., & Chen, Z. J. (2007) · Oncogene · doi:10.1038/sj.onc.1210413 · Cited by 455 · see citing works
Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1
Dibble, C. C., Asara, J. M., & Manning, B. D. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00735-09 · Cited by 420 · see citing works
TAK1 activates AMPK‐dependent cytoprotective autophagy in TRAIL‐treated epithelial cells
Herrero‐Martín, G., Høyer‐Hansen, M., García‐García, C., Fumarola, C., Farkas, T., López‐Rivas, A., & Jäättelä, M. (2009) · The EMBO Journal · doi:10.1038/emboj.2009.8 · Cited by 400 · see citing works
Siddique, T., Figlewigz, D. A., Pericak‐Vance, M. A., Haines, J. L., Rouleau, G. A., Jeffers, A. J., Sapp, P. C., Hung, W. ‐., Bebout, J., McKenna-Yasek, D. M., et al. (1991) · New England Journal of Medicine · doi:10.1056/nejm199105163242001 · Cited by 380 · see citing works
Cell type-specific function of TAK1 in innate immune signaling
Alagbala, A. A., Wang, H. Y., & Wang, R. (2013) · Trends in Immunology · doi:10.1016/j.it.2013.03.007 · Cited by 372 · see citing works
Zhang, X., Li, L., Chen, S., Yang, D., Wang, Y., Zhang, X., Wang, Z., & Le, W. (2011) · Autophagy · doi:10.4161/auto.7.4.14541 · Cited by 364 · see citing works
Xie, M., Zhang, D., Dyck, J. R. B., Li, Y., Zhang, H., Morishima, M., Mann, D. L., Taffet, G. E., Baldini, A., Khoury, D. S., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604708103 · Cited by 344 · see citing works
Self-citationTAK1 Mediates the Ceramide Signaling to Stress-activated Protein Kinase/c-Jun N-terminal Kinase
Shirakabe, K., Yamaguchi, T., Shibuyà, H., Irie, K., Matsuda, S., Moriguchi, T., Gotoh, Y., Matsumoto, K., & Nishida, E. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.13.8141 · Cited by 337 · see citing works
p70S6 Kinase Phosphorylates AMPK on Serine 491 to Mediate Leptin's Effect on Food Intake
Dagon, Y., Hur, E. E., Zheng, B., Wellenstein, K., Cantley, L. C., & Kahn, B. B. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.05.010 · Cited by 283 · see citing works
Saxena, S., Roselli, F., Singh, K., Leptien, K., Julien, J.-P., Gros-Louis, F., & Caroni, P. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.027 · Cited by 275 · see citing works
Rückemann-Dziurdzińska, K., Fairbanks, L. D., Carrey, E. A., Hawrylowicz, C. M., Richards, D. F., Kirschbaum, B. J., & Simmonds, H. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.34.21682 · Cited by 271 · see citing works
The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis
Imamura, K., Izumi, Y., Watanabe, A., Tsukita, K., Woltjen, K., Yamamoto, T., Hotta, A., Kondo, T., Kitaoka, S., Ohta, A., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf3962 · Cited by 260 · see citing works
Zhang, X., Chen, S., Song, L., Tang, Y., Shen, Y., Li, J. X., & Le, W. (2014) · Autophagy · doi:10.4161/auto.27710 · Cited by 256 · see citing works
Xu, X., Williams, J. W., Bremer, E. G., Finnegan, A., & Chong, A. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.21.12398 · Cited by 216 · see citing works
Self-citationSporadic and hereditary amyotrophic lateral sclerosis (ALS)
Ajroud‐Driss, S., & Siddique, T. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.08.010 · Cited by 205 · see citing works
Wang, W., Zhou, G., Hu, M. C. ‐., Yao, Z., & Tan, T. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.36.22771 · Cited by 188 · see citing works
REGULATION OF B CELL FUNCTION BY THE IMMUNOSUPPRESSIVE AGENT LEFLUNOMIDE1
Siemasko, K. F., Chong, A. S., Williams, J. W., Bremer, E. G., & Finnegan, A. (1996) · Transplantation · doi:10.1097/00007890-199602270-00020 · Cited by 183 · see citing works
Aguilar, V. M., Alliouachene, S., Sotiropoulos, A., Sobering, A. K., Athéa, Y., Djouadi, F., Miraux, S., Thiaudière, E., Foretz, M., Viollet, B., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.006 · Cited by 182 · see citing works
Inhibition of Dengue Virus through Suppression of Host Pyrimidine Biosynthesis
Wang, Q.-Y., Bushell, S. M., Qing, M., Xu, H. Y., Bonavia, A., Nunes, S., Zhou, J., Poh, M. K., de Sessions, P. F., Niyomrattanakit, P., et al. (2011) · Journal of Virology · doi:10.1128/jvi.02510-10 · Cited by 178 · see citing works
Self-citationTAK1, more than just innate immunity
Dai, L. X., Thu, C. A., Liu, X., Xi, J., & Cheung, P. (2012) · IUBMB Life · doi:10.1002/iub.1078 · Cited by 177 · see citing works
Elder, R. T., Xu, X., Williams, J. W., Gong, H., Finnegan, A., & Chong, A. S. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.1.22 · Cited by 174 · see citing works
Self-citationSiemasko, K. F., Chong, A. S., Jäck, H., Gong, H., Williams, J. W., & Finnegan, A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.4.1581 · Cited by 174 · see citing works
TAK1-mediated autophagy and fatty acid oxidation prevent hepatosteatosis and tumorigenesis
Inokuchi‐Shimizu, S., Park, E. J., Roh, Y. S., Yang, L., Zhang, B., Song, J., Liang, S., Pimienta, M., Taniguchi, K., Wu, X., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci74068 · Cited by 164 · see citing works
Coordinating TLR‐activated signaling pathways in cells of the immune system
Banerjee, A., & Gerondakis, S. (2007) · Immunology and Cell Biology · doi:10.1038/sj.icb.7100098 · Cited by 163 · see citing works
Goode, A., Butler, K., Long, J., Cavey, J., Scott, D., Shaw, B., Sollenberger, J., Gell, C., Johansen, T., Oldham, N. J., et al. (2016) · Autophagy · doi:10.1080/15548627.2016.1170257 · Cited by 153 · see citing works
Two activities of the immunosuppressive metabolite of leflunomide, A77 1726
Xu, X., Williams, J. W., Gong, H., Finnegan, A., & Chong, A. S. (1996) · Biochemical Pharmacology · doi:10.1016/0006-2952(96)00303-6 · Cited by 138 · see citing works
Self-citationTAK1 Participates in c-Jun N-Terminal Kinase Signaling during Drosophila Development
Takatsu, Y., Nakamura, M., Stapleton, M., Danos, M. C., Matsumoto, K., O’Connor, M. B., Shibuyà, H., & Ueno, N. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.9.3015-3026.2000 · Cited by 132 · see citing works
Common Molecular Pathways in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Weishaupt, J. H., Hyman, T., & Đikić, I. (2016) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2016.07.005 · Cited by 128 · see citing works
Protein folding alterations in amyotrophic lateral sclerosis
Parakh, S., & Atkin, J. D. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.010 · Cited by 111 · see citing works
Neuronal Tsc1/2 complex controls autophagy through AMPK-dependent regulation of ULK1
Nardo, A. D., Wertz, M. H., Kwiatkowski, E. R., Tsai, P. T., Leech, J. D., Greene-Colozzi, E. A., Goto, J., Dilsiz, P., Talos, D. M., Clish, C. B., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu101 · Cited by 109 · see citing works
IN VIVO ACTIVITY OF LEFLUNOMIDE
Chong, A. S., Huang, W., Liu, W., Luo, J., Shen, J., Xu, W. M., Ma, L., Blinder, L., Xiao, F., Xu, X., et al. (1999) · Transplantation · doi:10.1097/00007890-199907150-00020 · Cited by 98 · see citing works
Self-citationLi, Y., Guo, Y., wang, X., Yu, X., Duan, W., Hong, K., Wang, J., Han, H., & Li, C. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.03.061 · Cited by 98 · see citing works
Self-citationRegulation of the autophagy initiating kinase ULK1 by nutrients: Roles of mTORC1 and AMPK
Kim, J., & Guan, K. (2011) · Cell Cycle · doi:10.4161/cc.10.9.15291 · Cited by 96 · see citing works
Autophagy receptor defects and ALS-FTLD
Majcher, V., Goode, A., James, V. H., & Layfield, R. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.01.002 · Cited by 91 · see citing works
Xu, X., Blinder, L., Shen, J., Gong, H., Finnegan, A., Williams, J. W., & Chong, A. S. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.1.167 · Cited by 87 · see citing works
Self-citationRole of autophagy in the pathogenesis of amyotrophic lateral sclerosis
Lee, J. K., Shin, J. H., Lee, J. E., & Choi, E.-J. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2015.08.005 · Cited by 84 · see citing works
In vitro and in vivo antitumor activity of a novel immunomodulatory drug, leflunomide
Xu, X., Shen, J., Mall, J. W., Myers, J. A., Huang, W., Blinder, L., Saclarides, T. J., Williams, J. W., & Chong, A. S. (1999) · Biochemical Pharmacology · doi:10.1016/s0006-2952(99)00228-2 · Cited by 76 · see citing works
Self-citationWade, E. M., Daniel, P. B., Jenkins, Z. A., McInerney-Leo, A. M., Leo, P., Morgan, T., Addor, M. C., Adès, L. C., Bertola, D. R., Bohring, A., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.05.024 · Cited by 72 · see citing works
Chan, V., Charles, B. G., & Tett, S. E. (2005) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2005.02415.x · Cited by 57 · see citing works
Phosphatidylinositol 3‐Kinase: Increased Activity and Protein Level in Amyotrophic Lateral Sclerosis
Wagey, R. T. E., Pelech, S., Duronio, V., & Krieger, C. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.71020716.x · Cited by 52 · see citing works
Rosner, M., Schipany, K., & Hengstschläger, M. (2011) · Amino Acids · doi:10.1007/s00726-011-0965-4 · Cited by 52 · see citing works
Kim, J., Park, Y., Jang, Y., & Kwon, Y. H. (2011) · Brain Research · doi:10.1016/j.brainres.2011.08.059 · Cited by 51 · see citing works
Goff, C. L., Rogers, C. R., Goff, W. L., Pinto, G., Bonnet, D., Chrabieh, M., Alibeu, O., Nischké, P., Münnich, A., Pïcard, C., et al. (2016) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2016.06.005 · Cited by 47 · see citing works
Carunchio, I., Curcio, L., Pieri, M., Pica, F., Caioli, S., Viscomi, M. T., Molinari, M., Canu, N., Bernardi, G., & Zona, C. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.08.033 · Cited by 45 · see citing works
Zippel, N., Malik, R. A., Frömel, T., Popp, R., Bess, E., Strilić, B., Wettschureck, N., Fleming, I., & Fißlthaler, B. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.301848 · Cited by 43 · see citing works
Autophagy in motor neuron disease: Key pathogenetic mechanisms and therapeutic targets
Mis, M. S. C., Brajkovic, S., Frattini, E., Fonzo, A. D., & Corti, S. P. (2016) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2016.01.012 · Cited by 43 · see citing works
S6K1 Negatively Regulates TAK1 Activity in the Toll-Like Receptor Signaling Pathway
Kim, S. Y., Baik, K.-H., Baek, K., Chah, K.-H., Kim, K. A., Moon, G., Jung, E., Kim, S., Shim, J., Greenblatt, M. B., et al. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01225-13 · Cited by 42 · see citing works
Chen, Y., Huang, Q., Zhou, H., Wang, Y., Hu, X. M., & Li, T. (2016) · Oncotarget · doi:10.18632/oncotarget.10409 · Cited by 37 · see citing works
Doscas, M. E., Williamson, A. J., Usha, L., Bogachkov, Y. Y., Rao, G., Xiao, F., Wang, Y., Ruby, C. E., Kaufman, H. L., Zhou, J., et al. (2014) · Neoplasia · doi:10.1016/j.neo.2014.08.006 · Cited by 33 · see citing works
Self-citationFyn phosphorylates AMPK to inhibit AMPK activity and AMP-dependent activation of autophagy
Yamada, E., Okada, S., Bastie, C. C., Vatish, M., Nakajima, Y., Shibusawa, R., Ozawa, A., Pessin, J. E., & Yamada, M. (2016) · Oncotarget · doi:10.18632/oncotarget.11916 · Cited by 33 · see citing works
de Oliveira, G. P., Maximino, J. R., Maschietto, M. C., Zanoteli, E., Puga, R., Lima, L. A., Carraro, D. M., & Chadi, G. (2014) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-014-0029-x · Cited by 30 · see citing works
Xu, X., Sun, J. F., Song, R., Doscas, M. E., Williamson, A. J., Zhou, J., Sun, J., Jiao, X., Liu, X., & Li, Y. (2017) · Oncotarget · doi:10.18632/oncotarget.16737 · Cited by 30 · see citing works
Self-citationPark, J. S., Kang, D. H., Lee, D. H., & Bae, S. H. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.09.059 · Cited by 18 · see citing works
The role of trehalose for metastable state and functional form of recombinant interferon beta-1b
Fazeli, A., Shojaosadati, S. A., Fazeli, M. R., Khalifeh, K., Ariaeenejad, S., & Moosavi‐Movahedi, A. A. (2012) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2012.11.010 · Cited by 13 · see citing works
Flagged first, then by citations
1 of the 64 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,622 · see citing works
Self-citationWei, Q., Zhu, R., Zhu, J., Zhao, R., & Li, M. (2019) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504018x15462920753012 · Cited by 185 · see citing works
Regulation of the innate immune system by autophagy: neutrophils, eosinophils, mast cells, NK cells
Germič, N., Frangež, Ž., Yousefi, S., & Simon, H. (2019) · Cell Death and Differentiation · doi:10.1038/s41418-019-0295-8 · Cited by 111 · see citing works
Sun, X.-W., Wang, D.-Y., Zhang, T., Lu, X., Duan, F., Ju, L., Zhuang, X.-T., & Jiang, X.-C. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00084 · Cited by 103 · see citing works
Zou, L., Liao, M., Zhen, Y., Zhu, S., Chen, X., Zhang, J. C., Hao, Y., & Liu, B. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.06.004 · Cited by 100 · see citing works
Recent progress in the role of autophagy in neurological diseases
Meng, T., Lin, S., Zhuang, H., Huang, H., He, Z., Hu, Y., Gong, Q., & Feng, D. (2019) · Cell Stress · doi:10.15698/cst2019.05.186 · Cited by 58 · see citing works
Protein kinase inhibitors for amyotrophic lateral sclerosis therapy
Palomo, V., Nozal, V., Rojas‐Prats, E., Gil, C., & Martı́nez, A. (2020) · British Journal of Pharmacology · doi:10.1111/bph.15221 · Cited by 47 · see citing works
Exploring the Role of Autophagy Dysfunction in Neurodegenerative Disorders
Rana, T., Behl, T., Sehgal, A., Mehta, V., Singh, S., Bhatia, S., Al‐Harrasi, A., & BUNGAU, S. G. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02472-0 · Cited by 41 · see citing works
Hong, D., Zhang, C., Wu, W., Lu, X., & Zhang, L. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1133546 · Cited by 38 · see citing works
AMPK-Targeted Effector Networks in Mycobacterial Infection
Jo, E., Silwal, P., & Yuk, J. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.00520 · Cited by 38 · see citing works
CD24 blunts the sensitivity of retinoblastoma to vincristine by modulating autophagy
Sun, J., Feng, D., Xi, H., Luo, J., Zhou, Z., Liu, Q., Chen, Y., & Shao, Q. (2020) · Molecular Oncology · doi:10.1002/1878-0261.12708 · Cited by 34 · see citing works
Self-citationWang, N., Zhou, Y., Zhao, L., Wang, C.-D., Ma, W., Ge, G., Wang, Y., Ullah, I., Muhammad, F., Alwayli, D., et al. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111808 · Cited by 34 · see citing works
Liu, W., Zhuang, J., Jiang, Y., Sun, J. F., Prinz, R. A., Sun, J., Jiao, X., & Xu, X. (2019) · Cellular Microbiology · doi:10.1111/cmi.13095 · Cited by 33 · see citing works
Self-citationCasterton, R., Hunt, R. J., & Fanto, M. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.02.018 · Cited by 30 · see citing works
Liu, W. C., Zhu, S., Guo, Y., Tu, L., Zhen, Y., Zhao, R., Ouyang, L., Kurihara, H., He, R., & Liu, B. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00972-w · Cited by 31 · see citing works
Chen, J., Sun, J. F., Prinz, R. A., Li, Y., & Xu, X. (2018) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201800709 · Cited by 27 · see citing works
Self-citationMechanistic Insights into the Neuroprotective Potential of Sacred Ficus Trees
Shim, K. H., Sharma, N., & An, S. S. A. (2022) · Nutrients · doi:10.3390/nu14224731 · Cited by 21 · see citing works
Li, S., Wang, J., Lu, Y., Zhao, Y., Prinz, R. A., & Xu, X. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03744-2 · Cited by 21 · see citing works
Self-citationLiu, X., Zhang, J., Li, J., Song, C., & Shi, Y. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101536 · Cited by 20 · see citing works
Li, X., Sun, J. F., Prinz, R. A., Liu, X., & Xu, X. (2020) · Virology · doi:10.1016/j.virol.2020.06.009 · Cited by 19 · see citing works
Self-citationLi, Z., Chen, X., Chen, Y., Li, H., Yu, J., Li, Y., Zhu, W., Xie, Y., Tian, Y., Su, W., et al. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.113645 · Cited by 18 · see citing works
Self-citationYang, Q., Gao, L., Huang, X., Weng, J., Chen, Y., Lin, S., & Yin, Q. (2021) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2021.10412 · Cited by 16 · see citing works
Ciemiński, K., Flis, D. J., Dzik, K. P., Kaczor, J. J., Bialobrodzka, E. G., Hałoń, M., Wieckowski, M. R., Antosiewicz, J., & Ziółkowski, W. (2021) · Scientific Reports · doi:10.1038/s41598-021-00319-1 · Cited by 16 · see citing works
Beckers, J., & Damme, P. V. (2025) · Autophagy Reports · doi:10.1080/27694127.2025.2474796 · Cited by 16 · see citing works
Han, D., Kim, D., Kim, H., Lee, J., Lyu, J., Kim, J.-S., Shin, J., Kim, J. S., Kim, D. K., & Park, H. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1302227 · Cited by 17 · see citing works
Kaushal, J., Shukla, V., Sankhwar, P., Jha, R. K., & Dwivedi, A. (2021) · Cytokine · doi:10.1016/j.cyto.2021.155700 · Cited by 11 · see citing works
Chen, W., Yasen, M., Wang, H., Zhuang, C., Wang, Z., Lu, S., Jiang, L., & Lin, H. R. (2022) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-022-00633-y · Cited by 10 · see citing works
Sun, Y., Zhang, W., Men, L., Wu, J., Yao, L., Huang, X. X., Wu, Y., Zhang, C., Chen, Y., Carling, D., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01386-8 · Cited by 9 · see citing works
Zhuang, J., Ji, X., Zhu, Y., Liu, W., Sun, J. F., Jiao, X., & Xu, X. (2021) · Veterinary Microbiology · doi:10.1016/j.vetmic.2021.108982 · Cited by 9 · see citing works
Self-citationA system-wide mislocalization of RNA-binding proteins in motor neurons is a new feature of ALS
Liu, Y., Kuo, H., & Chern, Y. (2021) · Neurobiology of Disease · doi:10.1016/j.nbd.2021.105531 · Cited by 9 · see citing works
Wang, J., Hu, Y., Liu, P., & Xu, X. (2022) · The FASEB Journal · doi:10.1096/fj.202201436r · Cited by 8 · see citing works
Self-citationChua, V. Y. L., Lopez-Anton, M., Terai, M., Tanaka, R., Baqai, U., Purwin, T. J., Haj, J. I., Waltrich, F. J., Trachtenberg, I. V., Luo, K., et al. (2024) · Science Signaling · doi:10.1126/scisignal.adn8376 · Cited by 7 · see citing works
The contribution of proteasomal impairment to autophagy activation by C9orf72 poly-GA aggregates
Pu, M., Tai, Y., Yuan, L., Zhang, Y., Guo, H., Hao, Z., Chen, J., Qi, X., Wang, G., Tao, Z., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04518-5 · Cited by 8 · see citing works
Leflunomide alleviates obesity via activation of the TAK1‐AMPK pathway and induction of lipophagy
Ji, X., Chen, J., You, C., Sun, J. F., & Xu, X. (2023) · The FASEB Journal · doi:10.1096/fj.202301162r · Cited by 6 · see citing works
Self-citationHuo, D., Liang, W., Wang, D., Liu, Q., Wang, H., Wang, Y., Zhang, C., Cong, C., Su, X., Tan, X., et al. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109812 · Cited by 5 · see citing works
Xu, L., Bin, H., Zhou, Y., Liao, X., Chen, T., & He, H. (2025) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-025-01024-9 · Cited by 3 · see citing works
Vázquez-Bolado, A., Segundo, R. L.-S., García-Blanco, N., Rozalén, A. E., González-Álvarez, D., Suárez, M. B., Pérez-Hidalgo, L., & Moreno, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms24010148 · Cited by 2 · see citing works
Mechanisms of nanoparticle-induced autophagy disruption and its crosstalk with ferroptosis
Zhou, X., Zang, N., Jiang, C., & Jia, J. (2025) · Biomaterials Science · doi:10.1039/d5bm00821b · Cited by 1 · see citing works
Analisis funcional de PP2AB55 en ciclo celular, autofagia y transcripcion
Bolado, A. U. V. (2020) · doi:10.14201/gredos.145212
Linkage of proteasomal impairment and autophagy activation by C9orf72 poly-GA aggregate formationPreprint
Pu, M., Tai, Y., Yuan, L., Zhang, Y., Guo, H., Hao, Z., Chen, J., Qi, X., Wang, G., Tao, Z., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1481640/v1
Linkage of proteasomal impairment and autophagy activation by C9orf72 poly-GA aggregate formationPreprint
Pu, M., Tai, Y., Yuan, L., Zhang, Y., Guo, H., Hao, Z., Chen, J., Qi, X., Wang, G., Tao, Z., et al. (2022) · Research Square · doi:10.21203/rs.3.rs-1481640/v2
Mechanistic Insights into the Neuroprotective Effects of Natural Products in Diabetic Neuropathy
Ghosh, S., Warshi, D. H., Chowdhury, S. R., Rahaman, M., & Ghosh, S. (2024) · Current Bioactive Compounds · doi:10.2174/0115734072321268240920064955
Probing Allosteric Kinase Modulators as Next Game-Changers in Fighting Neurodegeneration
Roggiolani, E., Rosini, M., Minarini, A., & Basagni, F. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5c03783
- Authors
- Sun, J., Mu, Y., Jiang, Y., Song, R., Yi, J., Zhou, J., Sun, J., Jiao, X., Prinz, R. A., Li, Y., & Xu, X.
- Affiliations
- University of Illinois Chicago (US)
- Yangzhou University (CN)
- Kansas City University (US)
- Endeavor Health (US)
- Baylor College of Medicine (US)
- Rush University Medical Center (US)
- Corresponding author
- Xu, Xiulong
- ORCID
- Venue
- Cell Death & Disease
- Published
- 2018-03-14
- Volume
- 9
- Issue
- 3
- Pages
- 407-407
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC5851998
- OpenAlex
- W2793701057
- Cited by
- 44
- References
- 64
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 11 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 1
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Cell Death and Disease (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- U.S. Department of Defense
- Northwestern University
- National Natural Science Foundation of China (81672643)
- China Postdoctoral Science Foundation (BK20150450, 2015311, 2015M581873)
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province (2015M581873, 2015311, BK20150450)
- Yangzhou University
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR057404)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- A771726, leflunomide, autophagy, superoxide dismutase 1, amyotrophic lateral sclerosis, ULK1 phosphorylation, AMPK activation, TAK1, ATG7, protein degradation, motor neurons
- MeSH terms
- Autophagy-Related Protein-1 Homolog, Autophagy-Related Protein 7, Superoxide Dismutase-1, AMP-Activated Protein Kinase Kinases, MAP Kinase Kinase Kinase 7, Aniline Compounds, Animals, Autophagy, Cell Line, Crotonates, Hydroxybutyrates, Nitriles, Protein Kinases, Toluidines, Amino Acid Motifs, MAP Kinase Kinase Kinases, Ribosomal Protein S6 Kinases, 70-kDa, Mice, TOR Serine-Threonine Kinases, Proteolysis, Protein Aggregates
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