CD44 expression in astrocytes and microglia is associated with ALS progression in a mouse model
Abstract
Amyotrophic lateral sclerosis (ALS) is a motor neuron-specific neurodegenerative disease. An increasing body of evidence suggests that, in addition to cell autonomous regulation, i.e., pathological changes in motor neurons, non-cell autonomous mechanisms involving glial cells play critical roles in the pathogenesis of ALS. CD44 functions as a receptor for osteopontin and hyaluronan, and has been implicated in inflammation associated with neuronal injuries. However, this membrane glycoprotein has been poorly studied in ALS. Here we investigated its expression during ALS progression using SOD1(G93A) mice. CD44 expression increased around the onset of disease and then increased continuously. Astrocytes and microglia expressed CD44 in vivo. Consistent with these findings, primary cultured microglia began to express CD44 upon activation with LPS and interferon-γ. CD44 expression in primary cultured astrocytes was also enhanced by activation with interferon-γ+TNF-α or bFGF alone. As CD44 was detected in cell lysate, but not in culture media of astrocytes and microglia, it was likely that these glial cells expressed a membrane-bound form of CD44. Our study demonstrates that CD44 expression in astrocytes and microglia is closely associated with the pathogenesis of ALS, and suggests that inflammatory responses involving CD44 may play a role in this disease.
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In adult brain, CD44 expression is mainly restricted to astrocytes and activated microglia.
“CD44 expression in the adult brain is primarily confined to astrocytes and activated microglia”
From Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington's disease (2020) · cites this paper as Matsumoto et al., 2012
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Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670117
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670162
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Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670108
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670138
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670150
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670153
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670156
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670123
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670111
Martirosyan, A., Ansari, R. A., Pestana, F., Hebestreit, K., Gasparyan, H., Aleksanyan, R., Hnatova, S., Poovathingal, S. K., Marneffe, C., Thal, D. R., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26670168
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Microglia encapsulation in nanozyme-loaded hydrogels: response to oxidative stress and inflammation
Martín-Colomo, S., Ontoria, A., Tapeinos, C., Beloqui, A., Pineda, J. R., & Larrañaga, A. (2026) · Nanomedicine · doi:10.1080/17435889.2026.2667955
Mitochondrial microprotein MOCCI controls neuroinflammation by altering glial activation states
Shen, K., Guo, K., Leong, S. H., Lim, R., Chew, W. L., Lee, C. Q. E., & Ho, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1798798
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CD44 Knockout Alters the Cellular Response and Improves Locomotor Outcome After Spinal Cord Injury
Creasman, D. A., Benavente, F., Nishi, R. A., & Anderson, A. (2026) · ASN NEURO · doi:10.1080/17590914.2026.2673257
CD44 links glial activation to metabolic dysfunction in Alzheimer's disease
Kim, E., Lee, Y., Cho, Y. C., Lee, J., Kim, C. H., Kim, J., Baek, S. H., Kim, J. S., Cho, Y., Park, S., et al. (2026) · Genes & Diseases · doi:10.1016/j.gendis.2026.102474
- Authors
- Matsumoto, T., Imagama, S., Hirano, K., Ohgomori, T., Natori, T., Kobayashi, K., Muramoto, A., Ishiguro, N., & Kadomatsu, K.
- Affiliations
- Nagoya University (JP)
- Yamanashi Gakuin University (JP)
- Corresponding author
- Kadomatsu, Kenji
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 520
- Issue
- 1
- Pages
- 115-120
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2005347777
- Cited by
- 80
- References
- 27
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 21 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 4 · 2019: 7 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 6 · 2014: 2 · 2013: 4 · 2012: 1
- FWCI
- 2.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (18390099, 20390092)
- Ministry of Health, Labour and Welfare (H21-012)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Keywords
- CD44, amyotrophic lateral sclerosis, astrocytes, microglia, SOD1 G93A mice, non-cell autonomous neurodegeneration, glial inflammation, osteopontin, hyaluronic acid, interferon-gamma, lipopolysaccharide, TNF-α, basic fibroblast growth factor, microglial activation, disease progression
- MeSH terms
- Superoxide Dismutase-1, Amyotrophic Lateral Sclerosis, Animals, Astrocytes, Brain, Cells, Cultured, Disease Models, Animal, Mice, Transgenic, Spinal Cord, Superoxide Dismutase, Microglia, Hyaluronan Receptors, Mice
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