Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains
Open accessAbstract
The superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex of phagocytes (phox) plays a key role in production of reactive oxygen species (ROS) by microglia. The catalytic subunits of the NADPH oxidase are composed of p22phox and gp91phox. Nasu-Hakola disease (NHD) is a rare autosomal recessive disorder caused by a loss-of-function mutation of either TYROBP (DAP12) or TREM2. Pathologically, the brains of NHD patients exhibit extensive demyelination designated leukoencephalopathy, astrogliosis, accumulation of axonal spheroids, and remarkable activation of microglia predominantly in the white matter of frontal and temporal lobes. However, a pathological role of the gp91phox-p22phox complex in generation of leukoencephalopathy in NHD remains unknown. We clarified the expression of gp91phox and p22phox in the white matter of the frontal cortex derived from five NHD and eight control subjects. We identified the expression of p22phox and gp91phox immunoreactivity almost exclusively on microglia. Microglia overexpressed gp91phox in NHD brains and p22phox in myotonic dystrophy (MD) brains, when compared with non-neurological control (NC) brains. These results suggest that the enhanced expression of gp91phox by microglia might contribute to overproduction of ROS highly toxic to myelinating oligodendrocytes, resulting in oligodendrocyte cell death that induces leukoencephalopathy in NHD brains.
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ABI3 expression pattern overlapped with that of gp91phox, a marker of microglia.
“By double immunolabeling, the expression pattern of ABI3 overlapped with that of gp91phox, a marker of microglia (15) (Figure 5, panel a), whereas GFAP-positive astrocytes, CNPase-positive oligodendrocytes, and NeuN-positive neurons did not express ABI3 (Figure 5, panels b-d), suggesting that astrocytes, oligodendrocytes and neurons do not express discernible levels of ABI3”
From Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease (2017) · cites this paper as [15]
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Microglia express ABI3 in the brains of Alzheimer's disease and Nasu-Hakola disease
Satoh, J.-I., Kino, Y., Yanaizu, M., Tosaki, Y., Sakai, K., Ishida, T., & Saito, Y. (2017) · Intractable & Rare Diseases Research · doi:10.5582/irdr.2017.01073 · Cited by 55 · see citing works
Self-citation
- Authors
- Satoh, J.-I., Kino, Y., Yanaizu, M., Tosaki, Y., Sakai, K., Ishida, T., & Saito, Y.
- Affiliations
- Meiji Pharmaceutical University (JP)
- National Center for Global Health and Medicine (JP)
- National Center of Neurology and Psychiatry (JP)
- Venue
- Intractable & Rare Diseases Research
- Publisher
- International Research and Cooperation Association for Bio & Socio-Sciences Advancement (IRCA-BSSA)
- Published
- 2016
- Volume
- 5
- Issue
- 4
- Pages
- 275-279
- ISSN
- 2186-361X (ISSN-L)
- 2186-3644
- PMC
- PMC5116863
- OpenAlex
- W2547893774
- Cited by
- 13
- References
- 0
- Citations by year
- 2025: 1 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 2
- FWCI
- 0.91
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Intractable & Rare Diseases Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (S1511016, 16K07043)
- Ministry of Health, Labour and Welfare
- Japan Society for the Promotion of Science (25430054, C25430054, 16K07043)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Nasu-Hakola disease, gp91phox, p22phox, NADPH oxidase, microglia, leukoencephalopathy, reactive oxygen species, demyelination, myotonic dystrophy, oligodendrocyte death, TREM2, DAP12, white matter, frontal cortex
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