title: Ubiquitin-related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease.
abstract: Recent studies have shown that eosinophilic intranuclear inclusions (INI) in the brain of patients with intranuclear inclusion body disease (INIBD) are immunopositive for ubiquitin and ubiquitin-related proteins (URP). However, the extent and frequency of URP-immunoreactive inclusions in INIBD are uncertain. We immunohistochemically examined the brain, spinal cord and dorsal root ganglia from five patients with INIBD, using a virtual slide system with sequential staining of the same sections with hematoxylin and eosin and by immunolabeling with antibodies against ubiquitin and URP (NEDD8, NUB1, SUMO-1 and SUMO-2). Intranuclear inclusions were widely distributed in neurons and glial cells in all the cases. Sequential staining revealed that 100% of INI in neurons and glial cells were positive for ubiquitin. Moreover, the majority or a significant proportion of INI were positive for NEDD8, NUB1, SUMO-1 and SUMO-2. However, the proportions of NEDD8-, NUB1- and SUMO-1-positive inclusions were significantly higher in neurons than in glial cells (P < 0.05). These findings suggest that proteins related to ubiquitination and proteasomal degradation are involved in the formation of INI in INIBD.
authors.affiliation: Department of Neuropathology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan. neuropal@cc.hirosaki-u.ac.jp
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Mori
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Tanji
authors.forename: Saori
authors.initials: S
authors.lastname: Odagiri
authors.forename: Manabu
authors.initials: M
authors.lastname: Hattori
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Hoshikawa
authors.forename: Chikao
authors.initials: C
authors.lastname: Kono
authors.forename: Keizo
authors.initials: K
authors.lastname: Yasui
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yokoi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Tetsu
authors.initials: T
authors.lastname: Kamitani
authors.forename: Mari
authors.initials: M
authors.lastname: Yoshida
authors.forename: Koichi
authors.initials: K
authors.lastname: Wakabayashi
mesh_terms: D000368:Aged; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D006801:Humans; D045586:Intranuclear Inclusion Bodies / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex