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Cited by 358Amyotrophic Lateral Sclerosis ResearchEndoplasmic Reticulum Stress and DiseaseGenetic Neurodegenerative Diseases

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

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
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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.

Overview

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Crossref · 10.1093/brain/awm190

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72 of 72 references verified0 citation errors · 0 not checkable

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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)
ORCID
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
DOI
10.1093/brain/awm190
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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