The DOI matches its Crossref record; 72 of the 72 references it cites were found in a registry or an index.
Oxidative and endoplasmic reticulum stress interplay in sporadic amyotrophic lateral sclerosis
Abstract
The occurrence of endoplasmic reticulum (ER) stress in the sporadic form of amyotrophic lateral sclerosis (ALS) is unknown, despite it has been recently documented in experimental models of the familial form. Here we show that spinal cord from patients with sporadic ALS showed signs of ER stress, such as increased levels of ER chaperones such as protein-disulfide isomerase, and increased phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha). Among the potential causes of such ER stress proteasomal impairment was confirmed in the same samples by demonstrating increased ubiquitin immunoreactivity and increased protein lipoxidative (125%), glycoxidative (55%) and direct oxidative damage (62%) over control values, as evidenced by mass-spectrometry and immunological methods. We found that protein oxidative damage was strongly associated to ALS-specific changes in fatty acid concentrations, specifically of n-3 series (as docosahexaenoic acid), and in the amount of mitochondrial components as respiratory complexes I and III, suggesting a mitochondrial dysfunction leading to increased free radical production. Oxidative stress was also evidenced in frontal cortex, suggesting that this region is affected early in ALS. As those events were partially reproduced by threohydroxyaspartate exposure in organotypic spinal cord cultures, we concluded that changes in fatty acid composition, mitochondrial function and proteasome activity, which may be driven by excitotoxicity, lead to oxidative stress and finally contribute to ER stress in sporadic ALS.
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“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 [401]
In the citing paper
“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 [280]
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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 289
RetractedProduction of Reactive Oxygen Species by Mitochondria
Chen, Q., Vazquez, E. J., Moghaddas, S., Hoppel, C. L., & Lesnefsky, E. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304854200 · Cited by 1,616
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 1,476
Proteasome inhibitors induce a terminal unfolded protein response in multiple myeloma cells
Obeng, E. A., Carlson, L. M., Gutman, D. M., Harrington, W. J., Lee, K. P., & Boise, L. (2006) · Blood · doi:10.1182/blood-2005-08-3531 · Cited by 1,176
Hong, S., Gronert, K., Devchand, P. R., Moussignac, R.-L., & Serhan, C. N. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300218200 · Cited by 1,000
Endoplasmic Reticulum Stress Signaling in Disease
Marciniak, S. J., & Ron, D. (2006) · Physiological Reviews · doi:10.1152/physrev.00015.2006 · Cited by 951
ER stress and neurodegenerative diseases
Lindholm, D., Wootz, H., & Korhonen, L. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401778 · Cited by 882
Evidence of Increased Oxidative Damage in Both Sporadic and Familial Amyotrophic Lateral Sclerosis
Ferrante, R. J., Browne, S. E., Shinobu, L. A., Bowling, A. C., Baik, M. J., MacGarvey, U. M., Kowall, N. W., Brown, R. H., & Beal, M. F. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69052064.x · Cited by 808
Mitochondrial α-Ketoglutarate Dehydrogenase Complex Generates Reactive Oxygen Species
Starkov, A. A., Fiskum, G. M., Chinopoulos, C., Lorenzo, B. J., Browne, S. E., Patel, M. S., & Beal, M. F. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1899-04.2004 · Cited by 711
Grune, T., Jung, T., Merker, K., & Davies, K. J. A. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2004.04.020 · Cited by 666
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The Role of Endoplasmic Reticulum Stress in Human Pathology
Oakes, S. A., & Papa, F. R. (2014) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104649 · Cited by 1,621
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
Dash, U. C., Bhol, N. K., Swain, S. K., Samal, R. R., Nayak, P. K., Raina, V., Panda, S. K., Kerry, R. G., Duttaroy, A. K., & Jena, A. B. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.10.004 · Cited by 806
Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases
Hetz, C., & Mollereau, B. (2014) · Nature Reviews Neuroscience · doi:10.1038/nrn3689 · Cited by 684
Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health
Dumesic, D. A., Meldrum, D. R., Katz‐Jaffe, M. G., Krisher, R. L., & Schoolcraft, W. B. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.11.015 · Cited by 638
Metadata
- Authors
- Ilieva, E. V., Ayala, V., Jove, M., Dalfo, E., Cacabelos, D., Povedano, M., Bellmunt, M. J., Ferrer, I., Pamplona, R., & Portero-Otin, M.
- Affiliations
- Universitat de Lleida (ES)
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-03
- Volume
- 130
- Issue
- 12
- Pages
- 3111-3123
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2105174553
- Cited by
- 358
- References
- 72
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 21 · 2023: 15 · 2022: 17 · 2021: 14 · 2020: 17 · 2019: 20 · 2018: 13 · 2017: 23 · 2016: 15 · 2015: 26 · 2014: 23 · 2013: 21 · 2012: 28
- FWCI
- 13.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Clinical 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
- sporadic ALS, endoplasmic reticulum stress, oxidative stress, protein oxidation, protein disulfide isomerase, eIF2α phosphorylation, proteasome impairment, ubiquitin, docosahexaenoic acid, omega-3 fatty acids, mitochondrial dysfunction, respiratory chain complexes, frontal cortex, excitotoxicity, spinal cord
- MeSH terms
- Adult, Aged, Amyotrophic Lateral Sclerosis, Endoplasmic Reticulum, Fatty Acids, Female, Frontal Lobe, Humans, Male, Middle Aged, Mitochondria, Nerve Tissue Proteins, Organ Culture Techniques, Oxidation-Reduction, Spinal Cord, Oxidative Stress, Ubiquitin, Proteasome Endopeptidase Complex
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