Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders.
NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) is a ubiquitin-like protein that controls vital biological events through its conjugation to members of the cullin family, which are components of certain ubiquitin E3 ligases. Recent studies have shown that NEDD8 is incorporated into Lewy bodies (LBs) in Parkinson's disease, Mallory bodies in alcoholic liver disease and Rosenthal fibres in astrocytoma. In order to examine whether NEDD8 plays a role in the formation of ubiquitinated inclusions, we performed immunohistochemical staining of brain tissue from patients with various neurodegenerative disorders, using an affinity-purified polyclonal antibody raised against NEDD8 that did not cross-react with ubiquitin. In LB disease, NEDD8 immunoreactivity was present in almost all of the LBs and Lewy neurites. Moreover, NEDD8 immunoreactivity was found in a variety of ubiquitinated inclusions, including neuronal and oligodendroglial inclusions in multiple system atrophy, neurofibrillary tangles in Alzheimer's disease, ubiquitinated inclusions in motor neurone disease, and intranuclear inclusions in triplet repeat diseases. These findings suggest that NEDD8 is involved in the formation of various ubiquitinated inclusions via the ubiquitin-proteasome system.
Mori
F
F
Department of Neuropathology, Institute of Brain Science, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori 036-8562, Japan. neuropal@cc.hirosaki-u.ac.jp
Nishie
M
M
Piao
Y-S
YS
Kito
K
K
Kamitani
T
T
Takahashi
H
H
Wakabayashi
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D016631:Lewy Bodies / Q000378:metabolism; D008875:Middle Aged; D000075687:NEDD8 Protein; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009474:Neurons / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D014452:Ubiquitins / Q000378:metabolism*
D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins