Immunoreactivities of p62, an ubiqutin-binding protein, in the spinal anterior horn cells of patients with amyotrophic lateral sclerosis
Abstract
An ubiquitin-binding protein, p62, is one of the components of the ubiquitin-containing inclusions in several human neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is characterized by the presence of skein-like inclusions, Lewy body-like inclusions, and basophilic inclusions in the remaining anterior horn cells, in which these inclusions contain ubiquitin, while the other characteristic inclusions of Bunina type are ubiquitin-negative. We examined the spinal cord from 28 ALS cases including two ALS with dementia and two ALS with basophilic inclusions, using antibody to p62. The results demonstrated that p62 localized in skein-like inclusions, Lewy body-like inclusions and basophilic inclusions. The number of p62-positive inclusions observed in the remaining anterior horn cells of each section was variable among the ALS cases. In contrast, Bunina bodies, that do not contain ubiquitin, were negative for p62. As far as we examined, the 11 non-ALS cases did not show any p62 immunoreactivities in the anterior horn cells. Our results suggested that p62 plays important roles in forming the inclusions and may be associated with the protection of the neurons from degenerative processes involving ubiquitin.
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SQSTM1-positive inclusions are found in the majority of patients with ALS and FTD and often overlap with inclusions that stain for ubiquitin and TARDBP/TDP-43.
“Furthermore, SQSTM1-positive inclusions are found in the majority of patients with ALS and FTD, and often overlap with inclusions that stain for ubiquitin and TARDBP/TDP-43 (TAR DNA binding protein), an essential RNA-binding protein integrally connected with ALS-FTD [82,116–118] (Figure 1).”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [118]
SQSTM1-positive inclusions are also ubiquitin-positive, consistent with a disruption in the UPS.
“SQSTM1-positive inclusions are also ubiquitin-positive, consistent with a disruption in the UPS [118].”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [118]
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- Authors
- Mizuno, Y., Amari, M., Takatama, M., Aizawa, H., Mihara, B., & Okamoto, K.
- Affiliations
- Gunma University (JP)
- Asahikawa Medical College Hospital (JP)
- Institute of Brain and Blood Vessels (JP)
- Corresponding author
- Mizuno, Yuji
- Venue
- Journal of the Neurological Sciences
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 249
- Issue
- 1
- Pages
- 13-18
- ISSN
- 0022-510X (ISSN-L)
- OpenAlex
- W1970506744
- Cited by
- 158
- References
- 15
- Citations by year
- 2026: 7 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 13 · 2021: 14 · 2020: 15 · 2019: 8 · 2018: 10 · 2017: 9 · 2016: 6 · 2015: 12 · 2014: 9 · 2013: 4 · 2012: 7
- FWCI
- 3.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the Neurological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- p62, ubiquitin-binding protein, amyotrophic lateral sclerosis, Lewy body-like inclusions, Bunina bodies, neurodegeneration
- MeSH terms
- Sequestosome-1 Protein, Adult, Amyotrophic Lateral Sclerosis, Anterior Horn Cells, Inclusion Bodies, Female, Humans, Immunohistochemistry, Male, Middle Aged, Nerve Degeneration, Predictive Value of Tests, Proteins, Spinal Cord, Staining and Labeling, Lewy Bodies, Ubiquitin, Adaptor Proteins, Signal Transducing
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