XBP-1 deficiency in the nervous system protects against amyotrophic lateral sclerosis by increasing autophagy
Open accessAbstract
Mutations in superoxide dismutase-1 (SOD1) cause familial amyotrophic lateral sclerosis (fALS). Recent evidence implicates adaptive responses to endoplasmic reticulum (ER) stress in the disease process via a pathway known as the unfolded protein response (UPR). Here, we investigated the contribution to fALS of X-box-binding protein-1 (XBP-1), a key UPR transcription factor that regulates genes involved in protein folding and quality control. Despite expectations that XBP-1 deficiency would enhance the pathogenesis of mutant SOD1, we observed a dramatic decrease in its toxicity due to an enhanced clearance of mutant SOD1 aggregates by macroautophagy, a cellular pathway involved in lysosome-mediated protein degradation. To validate these observations in vivo, we generated mutant SOD1 transgenic mice with specific deletion of XBP-1 in the nervous system. XBP-1-deficient mice were more resistant to developing disease, correlating with increased levels of autophagy in motoneurons and reduced accumulation of mutant SOD1 aggregates in the spinal cord. Post-mortem spinal cord samples from patients with sporadic ALS and fALS displayed a marked activation of both the UPR and autophagy. Our results reveal a new function of XBP-1 in the control of autophagy and indicate critical cross-talk between these two signaling pathways that can provide protection against neurodegeneration.
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Antagonizing the unfolded protein response through deletion of XBP1 triggers autophagy and the clearance of SOD1 inclusions, delaying disease onset and improving survival.
“antagonizing the unfolded protein response (UPR) through deletion of XBP1 [335] triggers autophagy and the clearance of SOD1 inclusions, in the process delaying disease onset and improving survival.”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [335]
Genetic interventions that promote autophagy, such as the inactivation of the transcription factor XBP1 or restoration of HSPB8 expression in the nervous system, counteract ALS symptomatology by promoting the autophagy-dependent disposal of SOD1G93A.
“Conversely, genetic interventions that promote autophagy, such as the inactivation of the transcription factor XBP1 (X‐box binding protein 1) or restoration of HSPB8 expression in the nervous system, counteract ALS symptomatology by promoting the autophagy‐dependent disposal of SOD1G93A (Hetz et al, 2009; Crippa et al, 2010).”
From Autophagy in major human diseases (2021) · cites this paper as Hetz et al, 2009
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2 retracted
Atkin, J. D., Farg, M. A., Walker, A. K., McLean, C., Tomas, D., & Horne, M. K. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.02.009 · Cited by 350 · see citing works
RetractedAtkin, J. D., Farg, M. A., Turner, B. J., Tomas, D., Lysaght, J. A., Nunan, J., Rembach, A., Nagley, P., Beart, P. M., Cheema, S. S., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603393200 · Cited by 279 · see citing works
RetractedRepertoires 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
Autophagy in the Pathogenesis of Disease
Levine, B., & Kroemer, G. (2008) · Cell · doi:10.1016/j.cell.2007.12.018 · Cited by 7,069 · see citing works
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452 · see citing works
Self-citationSignal integration in the endoplasmic reticulum unfolded protein response
Ron, D., & Walter, P. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2199 · Cited by 6,308 · see citing works
Autophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,441 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · see citing works
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
Loss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
Induction of autophagy and inhibition of tumorigenesis by beclin 1
Liang, X. H., Jackson, S., Seaman, M., Brown, K., Kempkes, B., Hibshoosh, H., & Levine, B. (1999) · Nature · doi:10.1038/45257 · Cited by 3,347 · see citing works
Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T., & Ohsumi, Y. (2003) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-09-0704 · Cited by 2,323 · see citing works
Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
Klionsky, D. J., Abeliovich, H., Agostinis, P., Agrawal, D. K., Aliev, G., Askew, D. S., Baba, M., Baehrecke, E. H., Bahr, B. A., Ballabio, A., et al. (2008) · Autophagy · doi:10.4161/auto.5338 · Cited by 2,230 · see citing works
Self-citationLee, A., Iwakoshi, N. N., & Glimcher, L. H. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.21.7448-7459.2003 · Cited by 2,041 · see citing works
Self-citationThe roles of intracellular protein-degradation pathways in neurodegeneration
Rubinsztein, D. C. (2006) · Nature · doi:10.1038/nature05291 · Cited by 1,625 · see citing works
ALS: A Disease of Motor Neurons and Their Nonneuronal Neighbors
Boillée, S., Velde, C. V., & Cleveland, D. W. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.018 · Cited by 1,426 · see citing works
Kaser, A., Lee, A., Franke, A., Glickman, J. N., Zeißig, S., Tilg, H., Nieuwenhuis, E. E. S., Higgins, D. E., Schreiber, S., Glimcher, L. H., et al. (2008) · Cell · doi:10.1016/j.cell.2008.07.021 · Cited by 1,411 · see citing works
Self-citationPlasma cell differentiation requires the transcription factor XBP-1
Reimold, A., Iwakoshi, N., Manis, J., Vallabhajosyula, P., Szomolanyi-Tsuda, E., Gravallese, E., Friend, D., Grusby, M., Alt, F., & Glimcher, L. (2001) · Nature · doi:10.1038/35085509 · Cited by 1,371 · see citing works
Self-citationHDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS.
Pandey, U. B., Nie, Z., Batlevi, Y., McCray, B. A., Ritson, G. P., Nedelsky, N. B., Schwartz, S. L., DiProspero, N. A., Knight, M. A., Schuldiner, O., et al. (2007) · Nature · doi:10.1038/nature05853 · Cited by 1,234 · see citing works
Pickford, F., Masliah, E., Britschgi, M., Lucin, K. M., Narasimhan, R., Jaeger, P. A., Small, S., Spencer, B., Rockenstein, E., Levine, B., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci33585 · Cited by 1,186 · see citing works
Molecular biology of amyotrophic lateral sclerosis: insights from genetics
Pasinelli, P., & Brown, R. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1971 · Cited by 1,107 · see citing works
Self-citationRegulation of Hepatic Lipogenesis by the Transcription Factor XBP1
Lee, A., Scapa, E. F., Cohen, D. E., & Glimcher, L. H. (2008) · Science · doi:10.1126/science.1158042 · Cited by 978 · see citing works
Self-citationMisfolded proteins partition between two distinct quality control compartments
Kaganovich, D., Kopito, R., & Frydman, J. (2008) · Nature · doi:10.1038/nature07195 · Cited by 932 · see citing works
Ding, W.-X., Ni, H.-M., Gao, W., Yoshimori, T., Stolz, D. B., Ron, D., & Yin, X.-M. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070188 · Cited by 708 · see citing works
A role for motoneuron subtype–selective ER stress in disease manifestations of FALS mice
Saxena, S., Cabuy, E., & Caroni, P. (2009) · Nature Neuroscience · doi:10.1038/nn.2297 · Cited by 600 · see citing works
Nishitoh, H., Kadowaki, H., Nagai, A., Maruyama, T., Yokota, T., Fukutomi, H., Noguchi, T., Matsuzawa, A., Takeda, K., & Ichijo, H. (2008) · Genes & Development · doi:10.1101/gad.1640108 · Cited by 510 · see citing works
Role of EDEM in the Release of Misfolded Glycoproteins from the Calnexin Cycle
Molinari, M., Calanca, V., Galli, C., Lucca, P., & Paganetti, P. (2003) · Science · doi:10.1126/science.1079474 · Cited by 470 · see citing works
Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1
Shibata, M., Lu, T., Furuya, T., Degterev, A., Mizushima, N., Yoshimori, T., MacDonald, M., Yankner, B., & Yuan, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600364200 · Cited by 458 · see citing works
XBP‐1 is required for biogenesis of cellular secretory machinery of exocrine glands
Lee, A., Chu, G. C., Iwakoshi, N. N., & Glimcher, L. H. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600903 · Cited by 452 · see citing works
Self-citationProtective role of autophagy in neonatal hypoxia–ischemia induced brain injury
Carloni, S., Buonocore, G., & Balduini, W. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.07.022 · Cited by 444 · see citing works
Urushitani, M., Sik, A., Sakurai, T., Nukina, N., Takahashi, R., & Julien, J.-P. (2006) · Nature Neuroscience · doi:10.1038/nn1603 · Cited by 419 · see citing works
Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis
Ilieva, E. V., Ayala, V., Jove, M., Dalfo, E., Cacabelos, D., Povedano, M., Bellmunt, M. J., Ferrer, I., Pamplona, R., & Portero-Otin, M. (2007) · Brain · doi:10.1093/brain/awm190 · Cited by 358 · see citing works
Fujita, E., Kouroku, Y., Isoai, A., Kumagai, H., Misutani, A., Matsuda, C., Hayashi, Y. K., & Momoi, T. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm002 · Cited by 342 · see citing works
BAX Inhibitor-1 Is a Negative Regulator of the ER Stress Sensor IRE1α
Lisbona, F., Rojas‐Rivera, D., Thielen, P., Zamorano, S., Todd, D. J., Martinon, F., Glavic, Á., Kress, C. L., Lin, J. H., Walter, P., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.02.017 · Cited by 318 · see citing works
Self-citationKikuchi, H., Almer, G., Yamashita, S., Guégan, C., Nagai, M., Xu, Z., Sosunov, A. A., McKhann, G. M., & Przedborski, S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509227103 · Cited by 313 · see citing works
Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death
Rami, A., Langhagen, A., & Steiger, S. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2007.08.005 · Cited by 298 · see citing works
Impaired ERAD and ER stress are early and specific events in polyglutamine toxicityPreprint
Duennwald, M. L., & Lindquist, S. L. (2008) · Genes & Development · doi:10.1101/gad.1673408 · Cited by 296 · see citing works
Jaarsma, D., Teuling, E., Haasdijk, E. D., Zeeuw, C. I. D., & Hoogenraad, C. C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5258-07.2008 · Cited by 248 · see citing works
Court, F. A., Hendriks, W. T. J., MacGillavry, H. D., Álvarez, J., & van Minnen, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2429-08.2008 · Cited by 239 · see citing works
Self-citationIncreased autophagy in transgenic mice with a G93A mutant SOD1 gene
Morimoto, N., Nagai, M., Ohta, Y., Miyazaki, K., Kurata, T., Morimoto, M., Murakami, T., Takehisa, Y., Ikeda, Y., Kamiya, T., et al. (2007) · Brain Research · doi:10.1016/j.brainres.2007.06.045 · Cited by 223 · see citing works
Kabuta, T., Suzuki, Y., & Wada, K. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603337200 · Cited by 217 · see citing works
Closed Head Injury Induces Upregulation of Beclin 1 at the Cortical Site of Injury
Diskin, T., Tal‐Or, P., Erlich, S., Mizrachy, L., Alexandrovich, A. G., Shohami, E., & Pinkas‐Kramarski, R. (2005) · Journal of Neurotrauma · doi:10.1089/neu.2005.22.750 · Cited by 169 · see citing works
VAPB interacts with and modulates the activity of ATF6
Gkogkas, C. G., Middleton, S., Kremer, A., Wardrope, C., Hannah, M. J., Gillingwater, T. H., & Skehel, P. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn040 · Cited by 161 · see citing works
Suzuki, H., Kanekura, K., Levine, T. P., Kohno, K., Olkkonen, V. M., Aiso, S., & Matsuoka, M. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05857.x · Cited by 146 · see citing works
Hetz, C. A., Lee, A., Gonzalez-Romero, D., Thielen, P., Castilla, J., Soto, C. A., & Glimcher, L. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711094105 · Cited by 145 · see citing works
Self-citationMatus, S., Lisbona, F., Torres, M., Leon, C., Thielen, P., & Hetz, C. A. (2008) · Current Molecular Medicine · doi:10.2174/156652408784221324 · Cited by 128 · see citing works
Self-citationLepore, A. C., Haenggeli, C., Gasmi, M., Bishop, K. M., Bartus, R. T., Maragakis, N. J., & Rothstein, J. D. (2007) · Brain Research · doi:10.1016/j.brainres.2007.09.034 · Cited by 121 · see citing works
The RBCC GeneRFP2(Leu5) Encodes a Novel Transmembrane E3 Ubiquitin Ligase Involved in ERAD
Lerner, M., Corcoran, M., Cepeda, D., Nielsen, M. L., Zubarev, R. A., Pontén, F., Uhlén, M., Hober, S., Grandér, D., & Sangfelt, O. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-03-0248 · Cited by 109 · see citing works
Fine Structure of the Autophagosome
Eskelinen, E. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-157-4_2 · Cited by 108 · see citing works
Hetz, C. A., Thielen, P., Fisher, J. K., Pasinelli, P., Brown, R. H., Korsmeyer, S. J., & Glimcher, L. H. (2007) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402166 · Cited by 78 · see citing works
Self-citationStam, N. C., Nithianantharajah, J., Howard, M. L., Atkin, J. D., Cheema, S. S., & Hannan, A. J. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06374.x · Cited by 51 · see citing works
Flagged first, then by citations
1 of the 53 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The unfolded protein response: controlling cell fate decisions under ER stress and beyond
Hetz, C. A. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3270 · Cited by 4,118 · see citing works
Self-citationAutophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506 · see citing works
Mechanisms, regulation and functions of the unfolded protein response
Hetz, C., Zhang, K., & Kaufman, R. J. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0250-z · Cited by 2,666 · see citing works
Self-citationSelf-consumption: the interplay of autophagy and apoptosis
Mariño, G., Niso-Santano, M., Baehrecke, E. H., & Kroemer, G. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3735 · Cited by 2,172 · see citing works
Converging Mechanisms in ALS and FTD: Disrupted RNA and Protein Homeostasis
Ling, S.-C., Polymenidou, M., & Cleveland, D. W. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.033 · Cited by 1,811 · see citing works
Autophagy in major human diseases
Klionsky, D. J., Petroni, G., Amaravadi, R. K., Baehrecke, E. H., Ballabio, A., Boya, P., Bravo‐San Pedro, J. M., Cadwell, K., Cecconi, F., Choi, A. M. K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108863 · Cited by 1,585 · see citing works
Self-citationThe impact of the endoplasmic reticulum protein-folding environment on cancer development
Wang, M., & Kaufman, R. J. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3800 · Cited by 1,114 · see citing works
Autophagy and apoptosis dysfunction in neurodegenerative disorders
Ghavami, S., Shojaei, S., Yeganeh, B., Ande, S. R., Jangamreddy, J. R., Mehrpour, M., Christoffersson, J., Chaabane, W., Moghadam, A. R., Kashani, H. H., et al. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.004 · Cited by 1,039 · see citing works
ER stress and the unfolded protein response in neurodegeneration
Hetz, C. A., & Saxena, S. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.99 · Cited by 1,006 · see citing works
Self-citationThe impact of the unfolded protein response on human disease
Wang, S., & Kaufman, R. J. (2012) · The Journal of Cell Biology · doi:10.1083/jcb.201110131 · Cited by 983 · see citing works
Targeting the unfolded protein response in disease
Hetz, C. A., Chevet, É., & Harding, H. P. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3976 · Cited by 908 · see citing works
Self-citationThe unfolded protein response in immunity and inflammation
Grootjans, J., Kaser, A., Kaufman, R. J., & Blumberg, R. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.62 · Cited by 811 · see citing works
ER stress: Autophagy induction, inhibition and selection
Rashid, H.-O., Yadav, R. K., Kim, H., & Chae, H. (2015) · Autophagy · doi:10.1080/15548627.2015.1091141 · Cited by 796 · see citing works
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Hetz, C., & Mollereau, B. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3689 · Cited by 684 · see citing works
Self-citationMolecular pathways of motor neuron injury in amyotrophic lateral sclerosis
Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.152 · Cited by 615 · see citing works
Basic mechanisms of neurodegeneration: a critical update
Jellinger, K. A. (2010) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2010.01010.x · Cited by 608 · see citing works
The Unfolded Protein Response: Integrating Stress Signals Through the Stress Sensor IRE1α
Hetz, C. A., Martinon, F., Rodríguez, D. A., & Glimcher, L. H. (2011) · Physiological Reviews · doi:10.1152/physrev.00001.2011 · Cited by 568 · see citing works
Self-citationFighting neurodegeneration with rapamycin: mechanistic insights
Bové, J., Martínez‐Vicente, M., & Vila, M. (2011) · Nature reviews. Neuroscience · doi:10.1038/nrn3068 · Cited by 525 · see citing works
Ubiquitin-like protein conjugation and the ubiquitin–proteasome system as drug targets
Bedford, L., Lowe, J., Dick, L. R., Mayer, R. J., & Brownell, J. E. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3321 · Cited by 563 · see citing works
Mfn2 modulates the UPR and mitochondrial function via repression of PERK
Muñoz, J. P., Ivanova, S., Sánchez‐Wandelmer, J., Martínez‐Cristóbal, P., Noguera, E., Sancho, A., Díaz‐Ramos, A., Hernández‐Alvarez, M. I., Sebastián, D., Mauvezin, C., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.168 · Cited by 451 · see citing works
Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models
Barmada, S. J., Serio, A., Arjun, A., Bilican, B., Daub, A., Ando, D. M., Tsvetkov, A., Pleiss, M., Li, X., Peisach, D., et al. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1563 · Cited by 431 · see citing works
Endoplasmic reticulum dysfunction in neurological disease
Roussel, B. D., Kruppa, A. J., Miranda, E., Crowther, D. C., Lomas, D. A., & Marciniak, S. J. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(12)70238-7 · Cited by 441 · see citing works
Endoplasmic Reticulum Stress and Unfolded Protein Response in Neurodegenerative Diseases
Ghemrawi, R., & Khair, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176127 · Cited by 406 · see citing works
Targeting ER stress induced apoptosis and inflammation in cancer
Verfaillie, T., Garg, A. D., & Agostinis, P. (2010) · Cancer Letters · doi:10.1016/j.canlet.2010.07.016 · Cited by 392 · see citing works
Endoplasmic Reticulum Stress–Activated Cell Reprogramming in Oncogenesis
Chevet, É., Hetz, C. A., & Afshin Samali, A. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1490 · Cited by 386 · see citing works
Self-citationThe endoplasmic reticulum stress response in aging and age-related diseases
Brown, M. K., & Naidoo, N. N. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00263 · Cited by 372 · see citing works
The unfolded protein response in neurodegenerative diseases: a neuropathological perspective
Scheper, W., & Hoozemans, J. J. M. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1462-8 · Cited by 369 · see citing works
Liu, J., & Wang, F. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01005 · Cited by 376 · see citing works
Song, S., Tan, J., Miao, Y., & Zhang, Q. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.26137 · Cited by 361 · see citing works
Linking ER Stress to Autophagy: Potential Implications for Cancer Therapy
Verfaillie, T., Salazar‐Roa, M., Velasco, G., & Agostinis, P. (2010) · International Journal of Cell Biology · doi:10.1155/2010/930509 · Cited by 344 · see citing works
Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis
Dasuri, K., Zhang, L., & Keller, J. N. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.09.016 · Cited by 371 · see citing works
Castillo, K., Nassif, M., Valenzuela, V., Rojas, F., Matus, S., Mercado, G., Court, F. A., van Zundert, B., & Hetz, C. A. (2013) · Autophagy · doi:10.4161/auto.25188 · Cited by 338 · see citing works
Self-citationSalminen, A., Kauppinen, A., Suuronen, T., Kaarniranta, K., & Ojala, J. O. (2009) · Journal of Neuroinflammation · doi:10.1186/1742-2094-6-41 · Cited by 327 · see citing works
Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders
Doyle, K., Kennedy, D. C., Gorman, A. M., Gupta, S., Healy, S., & Samali, A. (2011) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2011.01374.x · Cited by 320 · see citing works
Emerging mechanisms of molecular pathology in ALS
Peters, O. M., Ghasemi, M., & Brown, R. H. (2015) · Journal of Clinical Investigation · doi:10.1172/jci71601 · Cited by 319 · see citing works
Self-citationMutant superoxide dismutase 1-induced IL-1β accelerates ALS pathogenesis
Meissner, F., Molawi, K., & Zychlinsky, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1002396107 · Cited by 319 · see citing works
Endoplasmic reticulum stress and inflammation in the central nervous system
Sprenkle, N. T., Sims, S. G., Sánchez, C. L., & Meares, G. P. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0183-y · Cited by 299 · see citing works
Vidal, R. L., Figueroa, A., Court, F. A., Thielen, P., Molina, C., Wirth, C., Caballero, B., Kiffin, R., Segura‐Aguilar, J., Cuervo, A. M., et al. (2012) · Human Molecular Genetics · doi:10.1093/hmg/dds040 · Cited by 281 · see citing works
Self-citationCalcium dysregulation in amyotrophic lateral sclerosis
Großkreutz, J., Bosch, L. V. D., & Keller, B. U. (2010) · Cell Calcium · doi:10.1016/j.ceca.2009.12.002 · Cited by 284 · see citing works
Johann, S., Heitzer, M., Kanagaratnam, M., Goswami, A., Rizo, T., Weis, J., Troost, D., & Beyer, C. (2015) · Glia · doi:10.1002/glia.22891 · Cited by 276 · see citing works
The ER stress factor XBP1s prevents amyloid-β neurotoxicity
Casas-Tinto, S., Zhang, Y., Sanchez-Garcia, J., Gomez-Velazquez, M., Rincon-Limas, D. E., & Fernandez-Funez, P. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr100 · Cited by 275 · see citing works
Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress
Deegan, S., Saveljeva, S., Gorman, A. M., & Samali, A. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1173-4 · Cited by 273 · see citing works
Modulating stress responses by the UPRosome: a matter of life and death.
Woehlbier, U., & Hetz, C. (2011) · TIBS -Trends in Biochemical Sciences. Regular ed · doi:10.1016/j.tibs.2011.03.001 · Cited by 269 · see citing works
Self-citationRoles of XBP1s in Transcriptional Regulation of Target Genes
Park, S.-M., Kang, T.-I., & So, J. (2021) · Biomedicines · doi:10.3390/biomedicines9070791 · Cited by 265 · see citing works
Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders
Cai, Y. C., Arikkath, J., Yang, L., Guo, M., Periyasamy, P., & Buch, S. J. (2016) · Autophagy · doi:10.1080/15548627.2015.1121360 · Cited by 258 · see citing works
Kolattukudy, P. E., & Niu, J. (2012) · Circulation Research · doi:10.1161/circresaha.111.243212 · Cited by 246 · see citing works
Nakka, V. P., Prakash-babu, P., & Vemuganti, R. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-9029-6 · Cited by 226 · see citing works
An unfolded protein-induced conformational switch activates mammalian IRE1
Karagöz, G. E., Acosta‐Alvear, D., Nguyen, H. T., Lee, C. P., Feixia Chu, C., & Walter, P. (2017) · eLife · doi:10.7554/elife.30700 · Cited by 238 · see citing works
Autophagy Induction as a Therapeutic Strategy for Neurodegenerative Diseases
Djajadikerta, A., Keshri, S., Tanasa, M. P., Prestil, R., Ryan, L., & Rubinsztein, D. C. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.035 · Cited by 238 · see citing works
Emerging roles of <scp>ER</scp> stress in the etiology and pathogenesis of Alzheimer's disease
Gerakis, Y., & Hetz, C. (2018) · The FEBS Journal · doi:10.1111/febs.14332 · Cited by 226 · see citing works
Self-citationAutophagy in Neurodegenerative Diseases: From Mechanism to Therapeutic Approach
Nah, J., Yuan, J., & Jung, Y. (2015) · Molecules and Cells · doi:10.14348/molcells.2015.0034 · Cited by 229 · see citing works
Crohn's disease: NOD2, autophagy and ER stress converge
Fritz, T. M. J., Niederreiter, L., Adolph, T. E., Blumberg, R. S., & Kaser, A. (2011) · Gut · doi:10.1136/gut.2009.206466 · Cited by 228 · see citing works
The role of endoplasmic reticulum stress in neurodegenerative disease
Xiang, C., Wang, Y., Zhang, H., & Han, F. (2016) · APOPTOSIS · doi:10.1007/s10495-016-1296-4 · Cited by 230 · see citing works
HLA-B27 misfolding and ankylosing spondylitis
Colbert, R. A., Tran, T. M., & Layh‐Schmitt, G. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.07.013 · Cited by 228 · see citing works
Autophagy in aging and neurodegenerative diseases: implications for pathogenesis and therapy
Tan, C., Yu, J., Tan, M., Jiang, T., Zhu, X., & Tan, L. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.11.019 · Cited by 221 · see citing works
Protein folding stress in neurodegenerative diseases: a glimpse into the ER
Matus, S., Glimcher, L. H., & Hetz, C. A. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2011.01.003 · Cited by 222 · see citing works
Self-citationControl of dopaminergic neuron survival by the unfolded protein response transcription factor XBP1
Valdés, P., Mercado, G., Vidal, R. L., Molina, C., Parsons, G., Court, F. A., Martinez, A. N., Galleguillos, D., Armentano, D., Schneider, B. L., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321845111 · Cited by 220 · see citing works
Self-citationER stress inhibits neuronal death by promoting autophagy
Fouillet, A., Levet, C., Virgone‐Carlotta, A., Robin, M., Dourlen, P., Rieusset, J., Belaïdi, E., Ovize, M., Touret, M., Nataf, S., et al. (2012) · Autophagy · doi:10.4161/auto.19716 · Cited by 220 · see citing works
Autophagy mediates pharmacological lifespan extension by spermidineand resveratrol
Morselli, E., Galluzzi, L., Kepp, O., Criollo, A., Maiuri, M. C., Tavernarakis, N., Madeo, F., & Kroemer, G. (2009) · Aging · doi:10.18632/aging.100110 · Cited by 213 · see citing works
Recent Insights into the Role of Unfolded Protein Response in ER Stress in Health and Disease
Lindholm, D., Korhonen, L., Eriksson, O., & Kõks, S. (2017) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2017.00048 · Cited by 214 · see citing works
IRE1 signaling exacerbates Alzheimer’s disease pathogenesis
Duran-Aniotz, C. A., Cornejo, V. H., Espinoza, S., Ardiles, Á. O., Medinas, D. B., Salazar, C., Foley, A., Gajardo, I., Thielen, P., Iwawaki, T., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1694-x · Cited by 210 · see citing works
Self-citationER stress and impaired autophagy flux in neuronal degeneration and brain injury
Yin, Y., Sun, G., Li, E., Kiselyov, K. I., & Sun, D. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.08.008 · Cited by 214 · see citing works
Luhr, M., Torgersen, M. L., Szalai, P., Hashim, A., Brech, A., Staerk, J., & Engedal, N. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002829 · Cited by 208 · see citing works
Endoplasmic reticulum proteostasis impairment in aging
Martínez, G., Duran-Aniotz, C. A., Cabral‐Miranda, F., Vivar, J. P., & Hetz, C. A. (2017) · Aging Cell · doi:10.1111/acel.12599 · Cited by 206 · see citing works
Self-citationAxonal Degeneration Is Mediated by the Mitochondrial Permeability Transition Pore
Barrientos, S. A., Martínez, N. W., Yoo, S., Jara, J. S., Zamorano, S., Hetz, C. A., Twiss, J. L., Álvarez, J., & Court, F. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4065-10.2011 · Cited by 207 · see citing works
Self-citationBohnert, K. R., McMillan, J. D., & Kumar, A. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25852 · Cited by 213 · see citing works
Cortés, C. J., & Spada, A. R. L. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.05.012 · Cited by 197 · see citing works
Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2
Ferguson, C. J., Lenk, G. M., & Meisler, M. H. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp460 · Cited by 202 · see citing works
Hu, Y., Park, K. K., Liu, Y., Wei, X., Yang, Q., Cho, K., Thielen, P., Lee, A.-H., Cartoni, R., Glimcher, L. H., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.026 · Cited by 201 · see citing works
Self-citationThe Autophagy Lysosomal Pathway and Neurodegeneration
Finkbeiner, S. (2020) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a033993 · Cited by 196 · see citing works
Autophagy and ALS: mechanistic insights and therapeutic implications
Chua, J. P., De Calbiac, H., Kabashi, E., & Barmada, S. J. (2022) · Autophagy · doi:10.1080/15548627.2021.1926656 · Cited by 189 · see citing works
“Furthermore, antagonizing the unfolded protein response (UPR) through deletion of XBP1 [335] triggers autophagy and the clearance of SOD1 inclusions, in the process delaying disease onset and improving survival.”
BackgroundInfluentialSun, S., Sun, Y., Ling, S., Ferraiuolo, L., McAlonis‐Downes, M., Zou, Y., Drenner, K., Wang, Y., Ditsworth, D., Tokunaga, S., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520639112 · Cited by 194 · see citing works
Autophagy in neurodegenerative disorders: pathogenic roles and therapeutic implications
Banerjee, R., Beal, M. F., & Thomas, B. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.09.001 · Cited by 199 · see citing works
Signaling Pathways from the Endoplasmic Reticulum and Their Roles in Disease
Kadowaki, H., & Nishitoh, H. (2013) · Genes · doi:10.3390/genes4030306 · Cited by 197 · see citing works
Walker, A. K., Soo, K. Y., Sundaramoorthy, V., Parakh, S., Ma, Y., Farg, M. A., Wallace, R. H., Crouch, P. J., Turner, B. J., Horne, M. K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081170 · Cited by 187 · see citing works
An ERcentric view of Parkinson's disease
Mercado, G., Valdés, P., & Hetz, C. A. (2013) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.12.005 · Cited by 185 · see citing works
Self-citationHypoxia and Selective Autophagy in Cancer Development and Therapy
Daskalaki, I., Gkikas, I., & Tavernarakis, N. (2018) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2018.00104 · Cited by 188 · see citing works
Targeting the IRE1α–XBP1 branch of the unfolded protein response in human diseases
Jiang, D., Niwa, M., & Koong, A. C. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.04.010 · Cited by 185 · see citing works
SQSTM1/p62: a potential target for neurodegenerative disease
Ma, S., Attarwala, I. Y., & Xie, X.-Q. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00516 · Cited by 185 · see citing works
Axonal Degeneration during Aging and Its Functional Role in Neurodegenerative Disorders
Salvadores, N., Sanhueza, M., Manque, P., & Court, F. A. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00451 · Cited by 182 · see citing works
Self-citationAutophagy and Neuronal Cell Death in Neurological DisordersPreprint
Nixon, R. A., & Yang, D.-S. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008839 · Cited by 179 · see citing works
Purkayastha, S., Zhang, H., Zhang, G., Ahmed, Z., Wang, Y., & Cai, D. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006875108 · Cited by 179 · see citing works
SOD1 Function and Its Implications for Amyotrophic Lateral Sclerosis Pathology
Bunton-Stasyshyn, R. K. A., Saccon, R. A., Fratta, P., & Fisher, E. (2014) · The Neuroscientist · doi:10.1177/1073858414561795 · Cited by 180 · see citing works
Cellular Mechanisms of Endoplasmic Reticulum Stress Signaling in Health and Disease. 1. An overview
Dufey, E., Sepúlveda, D., Rojas‐Rivera, D., & Hetz, C. A. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00258.2014 · Cited by 186 · see citing works
Self-citationRemondelli, P., & Renna, M. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00187 · Cited by 167 · see citing works
Lee, H., Noh, J.-Y., Oh, Y., Kim, Y., Chang, J.-W., Chung, C.-W., Lee, S.-T., Kim, M., Ryu, H., & Jung, Y.-K. (2012) · Human Molecular Genetics · doi:10.1093/hmg/ddr445 · Cited by 157 · see citing works
Regulation of Memory Formation by the Transcription Factor XBP1
Martínez, G., Vidal, R. L., Mardones, P., Serrano, F. G., Ardiles, A. O., Wirth, C., Valdés, P., Thielen, P., Schneider, B. L., Kerr, B., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.028 · Cited by 163 · see citing works
Self-citationThe Unfolded Protein Response and the Role of Protein Disulfide Isomerase in Neurodegeneration
Perri, E. R., Thomas, C. J., Parakh, S., Spencer, D. M. S., & Atkin, J. D. (2016) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2015.00080 · Cited by 164 · see citing works
Endoplasmic Reticulum Stress Interacts With Inflammation in Human Diseases
Cao, S. S., Luo, K. L., & Shi, L. (2015) · Journal of Cellular Physiology · doi:10.1002/jcp.25098 · Cited by 163 · see citing works
ER stress in skeletal muscle remodeling and myopathies
Afroze, D., & Kumar, A. (2017) · FEBS Journal · doi:10.1111/febs.14358 · Cited by 162 · see citing works
Adaptive Unfolded Protein Response Attenuates Alcohol-Induced Pancreatic Damage
Lugea, A., Tischler, D., Nguyen, J., Gong, J., Gukovsky, I., French, S. W., Gorelick, F. S., & Pandol, S. J. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.11.038 · Cited by 159 · see citing works
ATG5 regulates plasma cell differentiation
Conway, K. L., Kuballa, P., Khor, B., Zhang, M., Shi, H. N., Virgin, H. W., & Xavier, R. J. (2013) · Autophagy · doi:10.4161/auto.23484 · Cited by 154 · see citing works
Kaser, A., & Blumberg, R. S. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.02.048 · Cited by 152 · see citing works
Boivin, M., Pfister, V., Gaucherot, A., Ruffenach, F., Negroni, L., Sellier, C., & Charlet‐Berguerand, N. (2020) · The EMBO Journal · doi:10.15252/embj.2018100574 · Cited by 137 · see citing works
Targeting autophagy in neurodegenerative diseases
Vidal, R. L., Matus, S., Bargsted, L., & Hetz, C. A. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.09.002 · Cited by 145 · see citing works
Self-citationHomeostasis control in health and disease by the unfolded protein response
Acosta‐Alvear, D., Harnoss, J. M., Walter, P., & Ashkenazi, A. (2024) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-024-00794-0 · Cited by 139 · see citing works
Activation of the unfolded protein response enhances motor recovery after spinal cord injury
Hetz, C., Valenzuela, V., Collyer, E., Armentano, D., Parsons, G., & Court, F. A. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.8 · Cited by 141 · see citing works
Self-citationDigaleh, H., Kiaei, M., & Khodagholi, F. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1409-y · Cited by 137 · see citing works
Yang, M. H., Liu, J., Shao, J., Qin, Y., Ji, Q., Zhang, X., & Du, J. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-43 · Cited by 136 · see citing works
Beyond the cell factory: Homeostatic regulation of and by the UPR ER
Metcalf, M. G., Higuchi‐Sanabria, R., Garcia, G., Tsui, C. K., & Dillin, A. G. (2020) · Science Advances · doi:10.1126/sciadv.abb9614 · Cited by 131 · see citing works
- Authors
- Hetz, C., Thielen, P., Matus, S., Nassif, M., Court, F., Kiffin, R., Martinez, G., Cuervo, A. M., Brown, R. H., & Glimcher, L. H.
- Affiliations
- Harvard University (US)
- University of Chile (CL)
- Pontificia Universidad Católica de Chile (CL)
- Albert Einstein College of Medicine (US)
- Massachusetts General Hospital (US)
- ORCID
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-09-17
- Volume
- 23
- Issue
- 19
- Pages
- 2294-2306
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC2758741
- OpenAlex
- W2149927906
- Cited by
- 530
- References
- 53
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 17 · 2023: 15 · 2022: 25 · 2021: 32 · 2020: 28 · 2019: 28 · 2018: 35 · 2017: 43 · 2016: 46 · 2015: 48 · 2014: 35 · 2013: 44 · 2012: 44
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Americanae (AECID Library) (submittedVersion, other-oa)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Funders
- Michael J. Fox Foundation for Parkinson's Research
- ALS Association
- National Parkinson Foundation
- Muscular Dystrophy Association
- ALS Therapy Alliance
- Cure Huntington's Disease Initiative
- Broad Institute
- National Institutes of Health (AG031782)
- Parkinsonfonden
- Comisión Nacional de Investigación Científica y Tecnológica
- National Institute on Aging (P01AG031782, AG031782)
- National Institute of Allergy and Infectious Diseases (AI 32412, R01AI032412)
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (15010006)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- XBP1, amyotrophic lateral sclerosis, SOD1, unfolded protein response, endoplasmic reticulum stress, autophagy, macroautophagy, protein aggregate clearance, motor neurons, neuroprotection, transgenic mice, sporadic ALS, neurodegeneration
- MeSH terms
- Regulatory Factor X Transcription Factors, X-Box Binding Protein 1, Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Autophagy, DNA-Binding Proteins, Endoribonucleases, Female, Humans, Longevity, Male, Mice, Transgenic, Nervous System, Spinal Cord, Superoxide Dismutase, Transcription Factors, Up-Regulation, Protein Serine-Threonine Kinases, Mice, Gene Knockdown Techniques
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