Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice
Open accessAbstract
Endoplasmic reticulum (ER) stress-induced neuronal death may play a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). However, whether CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP), an ER-stress apoptotic mediator, is involved in the pathogenesis of ALS is controversial. Here we demonstrate the expression levels and localization of CHOP in spinal cords of both sporadic ALS patients and ALS transgenic mice by immunohistochemistry. In the spinal cords of sporadic ALS patients, CHOP was markedly up-regulated but typically expressed at low levels in those of the control. Likewise, CHOP expression increased at 14 (symptomatic stage) and 18 to 20 weeks (end stage) in ALS transgenic mice spinal cords. Furthermore, localizations of CHOP were merged in motor neurons and glial cells, such as oligodendrocytes, astrocytes, and microglia. These results indicate that the up-regulation of CHOP in motor neurons and glial cells may play pivotal roles in the pathogenesis of ALS.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Markers of oxidative stress, ER stress, and the UPR are upregulated in spinal cords and anterior horn cells from human patients with sALS.
“Markers of oxidative stress, ER stress, and the UPR are upregulated in spinal cords and anterior horn cells from human patients with sALS [277–280].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [277]
Cites
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
RetractedRosen, 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
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143 · see citing works
Roles of CHOP/GADD153 in endoplasmic reticulum stress
Oyadomari, S., & Mori, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401373 · Cited by 2,833 · see citing works
Mediators of endoplasmic reticulum stress-induced apoptosis
Szegezdi, E., Logue, S. E., Gorman, A. M., & Samali, A. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400779 · Cited by 2,345 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
From charcot to lou gehrig: deciphering selective motor neuron death in als
Cleveland, D. W., & Rothstein, J. D. (2001) · Nature reviews. Neuroscience · doi:10.1038/35097565 · Cited by 1,389 · see citing works
A trip to the ER: coping with stress
Rutkowski, D. T., & Kaufman, R. J. (2003) · Trends in Cell Biology · doi:10.1016/j.tcb.2003.11.001 · Cited by 1,364 · see citing works
Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220 · see citing works
Coupling endoplasmic reticulum stress to the cell death program
Rao, R. V., Ellerby, H. M., & Bredesen, D. E. (2004) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401378 · Cited by 1,208 · see citing works
Ron, D., & Habener, J. F. (1992) · Genes & Development · doi:10.1101/gad.6.3.439 · Cited by 1,156 · see citing works
Transcriptional and Translational Control in the Mammalian Unfolded Protein Response
Harding, H. P., Calfon, M. A., Urano, F., Novoa, I., & Ron, D. (2002) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.18.011402.160624 · Cited by 918 · see citing works
ER stress and neurodegenerative diseases
Lindholm, D., Wootz, H., & Korhonen, L. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401778 · Cited by 882 · see citing works
Regulation of apoptosis by endoplasmic reticulum pathways
Breckenridge, D. G., Germain, M., Mathai, J. P., Nguyen, M., & Shore, G. C. (2003) · Oncogene · doi:10.1038/sj.onc.1207108 · Cited by 742 · 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
Park, E., Velumian, A. A., & Fehlings, M. G. (2004) · Journal of Neurotrauma · doi:10.1089/0897715041269641 · Cited by 580 · 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
Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells
Matsumoto, M., Minami, M., Takeda, K., Sakao, Y., & Akira, S. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)01016-2 · Cited by 321 · see citing works
Nagai, M., Aoki, M., Miyoshi, I., Kato, M., Pasinelli, P., Kasai, N., Brown, R. H., & Itoyama, Y. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-23-09246.2001 · Cited by 318 · see citing works
Kikuchi, 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
Yamanaka, K., Boillee, S., Roberts, E. A., Garcia, M. L., McAlonis-Downes, M., Mikse, O. R., Cleveland, D. W., & Goldstein, L. S. B. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802556105 · Cited by 309 · see citing works
Phosphorylation of BCL‐2 regulates ER Ca2+ homeostasis and apoptosis
Bassik, M. C., Scorrano, L., Oakes, S. A., Pozzan, T., & Korsmeyer, S. J. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600104 · Cited by 278 · see citing works
Maytin, E. V., Ubeda, M., Lin, J. C., & Habener, J. F. (2001) · Experimental Cell Research · doi:10.1006/excr.2001.5248 · Cited by 244 · see citing works
Wei, H., Kim, S., Zhang, Z., Tsai, P., Wisniewski, K. E., & Mukherjee, A. B. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm324 · Cited by 209 · see citing works
Spinal cord injury induces endoplasmic reticulum stress with different cell‐type dependent response
Penas, C., Guzmán, M. T. O., Verdú, E., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04671.x · Cited by 169 · see citing works
ER Stress and Unfolded Protein Response in Amyotrophic Lateral Sclerosis
Kanekura, K., Suzuki, H., Aiso, S., & Matsuoka, M. (2009) · Molecular Neurobiology · doi:10.1007/s12035-009-8054-3 · Cited by 160 · see citing works
The ASK1-MAP Kinase Signaling in ER Stress and Neurodegenerative Diseases
Sekine, Y., Takeda, K., & Ichijo, H. (2006) · Current Molecular Medicine · doi:10.2174/156652406775574541 · Cited by 142 · see citing works
Kieran, D., Woods, I., Villunger, A., Strasser, A., & Prehn, J. H. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707906105 · Cited by 129 · see citing works
Tobisawa, S., Hozumi, Y., Arawaka, S., Koyama, S., Wada, M., Nagai, M., Aoki, M., Itoyama, Y., Goto, K., & Kato, T. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00353-x · Cited by 122 · see citing works
Wootz, H., Hansson, I., Korhonen, L., Näpänkangas, U., & Lindholm, D. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.07.118 · Cited by 111 · see citing works
Vlug, A. S., Teuling, E., Haasdijk, E. D., et al. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.04389.x · Cited by 110 · see citing works
Eymin, B., Dubrez, L., Allouche, M., & Solary, É. (1997) · PubMed · Cited by 97 · see citing works
Nagata, T., Ilieva, H. S., Murakami, T., Shiote, M., Narai, H., Ohta, Y., Hayashi, T., Shoji, M., & Abe, K. (2007) · Neurological Research · doi:10.1179/016164107x229803 · Cited by 77 · see citing works
ER Stress and UPR in Familial Amyotrophic Lateral Sclerosis
Turner, B. J., & Atkin, J. D. (2006) · Current Molecular Medicine · doi:10.2174/156652406775574550 · Cited by 59 · see citing works
Oyanagi, K., Yamazaki, M., Takahashi, H., et al. (2008) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2008.00941.x · Cited by 58 · see citing works
Self-citationLane, M., Ludwig, T. E., & Bavister, B. D. (1999) · Molecular Reproduction and Development · doi:10.1002/(sici)1098-2795(199912)54:4 · Cited by 27 · see citing works
Protein quality control in the endoplasmic reticulum.
Jørgensen, M. M., Bross, P., & Gregersen, N. (2003) · PubMed · Cited by 12 · see citing works
NO-induced apoptosis and ER stress in microglia
Kawahara, K., Mori, M., & Nakayama, H. (2004) · Folia Pharmacologica Japonica · doi:10.1254/fpj.124.399 · Cited by 11 · see citing works
Protein Quality Control in Endoplasmic Reticulum
Jørgensen, M. M., Bross, P., & Gregersen, N. (2003) · Apmis · Cited by 10 · see citing works
[ALS and microglia--a player for non-cell-autonomous neuron death].
Yamanaka, K., & Yamashita, H. (2007) · PubMed · Cited by 8 · see citing works
Protein quality control in the endoplasmic reticulum (472.3)
Ploegh, H. L. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.472.3 · Cited by 4 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
Mallucci, G. R., Klenerman, D., & Rubinsztein, D. C. (2020) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-040320-120625 · Cited by 62 · see citing works
Bowerman, M., Vincent, T., Scamps, F., Perrin, F. E., Camu, W., & Raoul, C. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00214 · Cited by 46 · see citing works
- Authors
- Ito, Y., Yamada, M., Tanaka, H., Aida, K., Tsuruma, K., Shimazawa, M., Hozumi, I., Inuzuka, T., Takahashi, H., & Hara, H.
- Affiliations
- Gifu Pharmaceutical University (JP)
- Saigata National Hospital (JP)
- Gifu University (JP)
- Brain Research Institute, Niigata University (JP)
- Corresponding author
- Hara, Hideaki
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2009-12
- Volume
- 36
- Issue
- 3
- Pages
- 470-476
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2054327578
- Cited by
- 141
- References
- 42
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 9 · 2023: 12 · 2022: 10 · 2021: 10 · 2020: 10 · 2019: 7 · 2018: 5 · 2017: 11 · 2016: 7 · 2015: 9 · 2014: 8 · 2013: 7 · 2012: 6
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (20·10786)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Keywords
- CHOP, endoplasmic reticulum stress, amyotrophic lateral sclerosis, sporadic ALS, motor neurons, glial cells, oligodendrocytes, astrocytes, microglia, neuronal cell death, spinal cord, ALS pathogenesis
- MeSH terms
- Superoxide Dismutase-1, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Animals, Astrocytes, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Middle Aged, Motor Neurons, Neuroglia, Oligodendroglia, Spinal Cord, Superoxide Dismutase, Microglia, Mice, Transcription Factor CHOP
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review