title: Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains.
abstract: 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 eitherTYROBP(DAP12) orTREM2. 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.
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Satoh
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kino
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Yanaizu
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Tosaki
authors.affiliation: Department of Bioinformatics and Molecular Neuropathology, Meiji Pharmaceutical University, Tokyo, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Pathology and Laboratory Medicine, Kohnodai Hospital, NCGM, Chiba, Japan.
authors.forename: Tusyoshi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Laboratory Medicine, National Center Hospital, NCNP, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Saito
keywords: Nasu-Hakola disease; gp91phox; leukoencephalopathy; microglia; p22phox