RETRACTED: Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis
Open accessAbstract
The unfolded protein response (UPR) is induced at symptom onset and disease end stage in rodent models of familial amyotrophic lateral sclerosis (ALS) that express superoxide dismutase (SOD1) mutations. However, ninety percent of human ALS is sporadic and mutations in SOD1 account for only 2% of total ALS. Here we show that a full UPR, including induction of stress sensor kinases, chaperones and apoptotic mediators, is also present in spinal cords of human patients with sporadic disease. Furthermore, the UPR chaperone protein disulphide isomerase (PDI) was present in CSF and was aggregated and widely distributed throughout the motor neurons of these patients. We also show up-regulation of UPR prior to the onset of symptoms in SOD1 rodents, implying an active role in disease. This study offers new insights into pathogenesis, placing ER stress onto a generic pathophysiology for 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?
IRE1α activation and UPR induction are present in postmortem brain and spinal cord tissues in AD, PD and ALS.
“Moreover, IRE1α activation and UPR induction are present in postmortem brain and spinal cord tissues in AD [398], PD [399] and ALS [400].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [400]
Spinal cord segments from autopsy of patients with sporadic ALS show ER stress resulting in induction of UPR, chaperones, and apoptotic markers.
“Additionally, spinal cord segments from autopsy of patients with sporadic ALS show ER stress resulting in the induction of UPR, chaperones, and apoptotic markers [400,401].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [400]
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 [278]
Cites
1 retracted
Atkin, 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
Self-citationRetractedRosen, 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
Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β
Nakagawa, T., Zhu, H., Morishima, N., Li, E., Xu, J., Yankner, B. A., & Yuan, J. (2000) · Nature · doi:10.1038/47513 · Cited by 3,262 · see citing works
Urano, F., Wang, X.-Z., Bertolotti, A., Zhang, Y.-H., Chung, P., Harding, H., & Ron, D. (2000) · Science · doi:10.1126/science.287.5453.664 · Cited by 3,081 · 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
Aggresomes: A Cellular Response to Misfolded Proteins
Johnston, J. A., Ward, C. L., & Kopito, R. R. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.143.7.1883 · Cited by 2,148 · 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
Amyotrophic lateral sclerosis is a distal axonopathy: evidence in mice and man
Fischer, L. R., Culver, D. G., Tennant, P., Davis, A. A., Wang, M.-S., Castellano-Sanchez, A. A., Khan, J., Polak, M. A., & Glass, J. D. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2003.10.004 · Cited by 1,338 · see citing works
Orchestrating the unfolded protein response in health and disease
Kaufman, R. J. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216886 · Cited by 1,015 · see citing works
S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration
Uehara, T., Nakamura, T., Yao, D., Shi, Z., Gu, Z., Ma, Y., Masliah, E., Nomura, Y., & Lipton, S. A. (2006) · Nature · doi:10.1038/nature04782 · Cited by 908 · see citing works
Involvement of caspase-4 in endoplasmic reticulum stress-induced apoptosis and Aβ-induced cell death
Hitomi, J., Katayama, T., Eguchi, Y., Kudo, T., Taniguchi, M., Koyama, Y., Manabe, T., Yamagishi, S., Bandô, Y., Imaizumi, K., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200310015 · Cited by 831 · see citing works
Johnston, J. A., Dalton, M. J., Gurney, M. E., & Kopito, R. R. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220417997 · Cited by 607 · see citing works
Ryu, E. J., Harding, H. P., Angelastro, J. M., Vitolo, O. V., Ron, D., & Greene, L. A. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-24-10690.2002 · Cited by 572 · see citing works
Proteins of the PDI family: Unpredicted non‐ER locations and functions
Turano, C., Coppari, S., Fabio Altieri, F., & Ferraro, A. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10172 · Cited by 520 · see citing works
Deng, H., Shi, Y., Furukawa, Y., Zhai, H., Fu, R., Liu, E., Gorrie, G., Khan, M. S., Hung, W.-Y., Bigio, E. H., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602046103 · Cited by 432 · 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
UBIQUITIN-IMMUNOREACTIVE INTRANEURONAL INCLUSIONS IN AMYOTROPHIC LATERAL SCLEROSIS
Leigh, P. N., Whitwell, H., Garofalo, O., Buller, J., Swash, M., Martin, J., Gallo, J., Weller, R. O., & Anderton, B. H. (1991) · Brain · doi:10.1093/brain/114.2.775 · Cited by 331 · 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
Tanaka, S., Uehara, T., & Nomura, Y. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.14.10388 · Cited by 267 · see citing works
Ezzi, S. A., Urushitani, M., & Julien, J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04531.x · Cited by 248 · see citing works
Furukawa, Y., Fu, R., Deng, H., Siddique, T., & O’Halloran, T. V. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602048103 · Cited by 225 · 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
Kanekura, K., Nishimoto, I., Aiso, S., & Matsuoka, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605049200 · Cited by 217 · see citing works
Piao, Y., Wakabayashi, K., Kakita, A., Yamada, M., Hayashi, S., Morita, T., Ikuta, F., Oyanagi, K., & Takahashi, H. (2003) · Brain Pathology · doi:10.1111/j.1750-3639.2003.tb00002.x · Cited by 210 · see citing works
The Disulfide Isomerase Grp58 Is a Protective Factor against Prion Neurotoxicity
Hetz, C. A., Russelakis‐Carneiro, M., Wälchli, S., Carboni, S., Vial-Knecht, E., Maundrell, K., Castilla, J., & Soto, C. A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4090-04.2005 · Cited by 197 · see citing works
Turner, B. J., Atkin, J. D., Farg, M. A., Zang, D. W., Rembach, A., Lopes, E. C., Patch, J. D., Hill, A. F., & Cheema, S. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4253-04.2005 · Cited by 193 · see citing works
Self-citationZhang, F., Ström, A., Fukada, K., Lee, S., Hayward, L. J., & Zhu, H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m609743200 · Cited by 181 · see citing works
Tortarolo, M., Veglianese, P., Calvaresi, N., Botturi, A., Rossi, C., Giorgini, A., Migheli, A., & Bendotti, C. (2003) · Molecular and Cellular Neuroscience · doi:10.1016/s1044-7431(03)00022-8 · Cited by 180 · see citing works
Matsumoto, G., Stojanovic, A., Holmberg, C. I., Kim, S., & Morimoto, R. I. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200504050 · Cited by 162 · see citing works
Shibata, N., Hirano, A., Kobayashi, M., Sasaki, S., Kato, T., Matsumoto, S., Shiozawa, Z., Komori, T., Ikemoto, A., Umahara, T., et al. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90956-3 · Cited by 151 · see citing works
Fragmentation of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis.
(1992) · PubMed Central · Cited by 150 · see citing works
Conn, K. J., Gao, W., McKee, A. C., Lan, M. S., Ullman, M. D., Eisenhauer, P. B., Fine, R. E., & Wells, J. M. (2004) · Brain Research · doi:10.1016/j.brainres.2004.07.026 · Cited by 144 · see citing works
Lowry, K., Murray, S. S., McLean, C., Talman, P. S., Mathers, S., Lopes, E., & Cheema, S. (2001) · Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders · doi:10.1080/146608201753275463 · Cited by 120 · see citing works
Self-citationYoo, B. C., Krapfenbauer, K., Cairns, N. J., Belay, G., Bajo, M., & Lübec, G. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)01071-6 · Cited by 90 · see citing works
The Golgi apparatus of moptor neurons in amyotrophic lateral sclerosis
Mourelatos, Z., Yachnis, A. T., RORKE, L. B., Mikol, J., & Gonatas, N. K. (1993) · Annals of Neurology · doi:10.1002/ana.410330609 · Cited by 45 · see citing works
Chou, S. M., Han, C. Y., Wang, H. S., et al. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00222-1 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The integrated stress response: From mechanism to disease
Costa-Mattioli, M., & Walter, P. (2020) · Science · doi:10.1126/science.aat5314 · Cited by 1,617 · see citing works
Islet Amyloid Polypeptide, Islet Amyloid, and Diabetes Mellitus
Westermark, P., Andersson, A., & Westermark, G. T. (2011) · Physiological Reviews · doi:10.1152/physrev.00042.2009 · Cited by 1,044 · see citing works
Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications
Almanza, A., Carlesso, A., Chintha, C., Creedican, S., Doultsinos, D., Leuzzi, B., Luís, A., McCarthy, N., Montibeller, L., More, S., et al. (2019) · The FEBS Journal · doi:10.1111/febs.14608 · Cited by 1,034 · see citing works
The unfolded protein response signals through high-order assembly of Ire1
Korennykh, A. V., Egea, P. F., Korostelev, A. A., Finer-Moore, J., Zhang, C., Shokat, K. M., Stroud, R. M., & Walter, P. (2009) · Nature · doi:10.1038/nature07661 · Cited by 656 · see citing works
Molecular 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
Moreno, J. A., Halliday, M., Molloy, C., Radford, H., Verity, N., Axten, J. M., Ortori, C. A., Willis, A. E., Fischer, P. M., Barrett, D. A., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006767 · Cited by 589 · see citing works
Hetz, C., Thielen, P., Matus, S., Nassif, M., Court, F., Kiffin, R., Martinez, G., Cuervo, A. M., Brown, R. H., & Glimcher, L. H. (2009) · Genes & Development · doi:10.1101/gad.1830709 · Cited by 530 · 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
Stutzbach, L. D., Xie, S. X., Naj, A. C., Albin, R., Gilman, S., PSP Genetics Study Group, Lee, V. M. Y., Trojanowski, J. Q., Devlin, B., & Schellenberg, G. D. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-31 · Cited by 197 · see citing works
Metabolomics of Human Brain Aging and Age-Related Neurodegenerative Diseases
Jové, M., Portero-Otín, M., Naudí, A., Ferrer, I., & Pamplona, R. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000091 · Cited by 195 · see citing works
The Complex Molecular Biology of Amyotrophic Lateral Sclerosis (ALS)
Redler, R. L., & Dokholyan, N. V. (2012) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-385883-2.00002-3 · Cited by 172 · see citing works
Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice
Ito, Y., Yamada, M., Tanaka, H., Aida, K., Tsuruma, K., Shimazawa, M., Hozumi, I., Inuzuka, T., Takahashi, H., & Hara, H. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.08.013 · Cited by 141 · see citing works
Sasaki, S. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181d44992 · Cited by 121 · 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
Thams, S., Lowry, E. R., Larraufie, M.-H., Spiller, K. J., Li, H., Williams, D. J., Hoang, P., Jiang, E., Williams, L. A., Sandoe, J., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2018.10.010 · Cited by 51 · see citing works
De Masi, R., & Orlando, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137373 · Cited by 20 · see citing works
“stress resulting in the induction of UPR, chaperones, and apoptotic markers [400,401].”
Influential
- Authors
- Atkin, J. D., Farg, M. A., Walker, A. K., McLean, C., Tomas, D., & Horne, M. K.
- Affiliations
- The University of Melbourne (AU)
- The Alfred Hospital (AU)
- Corresponding author
- Atkin, Julie D.
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 30
- Issue
- 3
- Pages
- 400-407
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2160059242
- Cited by
- 350
- References
- 38
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 13 · 2021: 18 · 2020: 24 · 2019: 30 · 2018: 22 · 2017: 22 · 2016: 26 · 2015: 38 · 2014: 25 · 2013: 23 · 2012: 28
- FWCI
- 13.78
- Type
- journal article
- Language
- en
- Status
- Retracted
- 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
- Victorian Brain Bank
- 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
- endoplasmic reticulum stress, unfolded protein response, sporadic ALS, SOD1 G93A mice, ATF6
- MeSH terms
- Superoxide Dismutase-1, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Animals, Endoplasmic Reticulum, Female, Humans, Male, Mice, Transgenic, Middle Aged, Superoxide Dismutase, Rats, Sprague-Dawley, Protein Folding, Oxidative Stress, Animals, Genetically Modified, Mice, Rats
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
