Cited by 141Amyotrophic Lateral Sclerosis ResearchEndoplasmic Reticulum Stress and DiseaseGenetic Neurodegenerative Diseases

Involvement of CHOP, an ER-stress apoptotic mediator, in both human sporadic ALS and ALS model mice

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Ito, Yasushi, Yamada, Mitsunori, Tanaka, Hirotaka, Aida, Kazunari, Tsuruma, Kazuhiro, Shimazawa, Masamitsu, Hozumi, Isao, Inuzuka, Takashi +2 more·2009·Neurobiology of Disease

Abstract

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.

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Crossref · 10.1016/j.nbd.2009.08.013

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  • 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].”

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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
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
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

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