Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders
Accumulation of NEDD8 in neuronal and glial inclusions of neurodegenerative disorders
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DOI：
10.1111/j.1365-2990.2004.00603.x
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发表时间：
2005-02-01
影响因子：
5
通讯作者：
Wakabayashi, K
中科院分区：
文献类型：
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作者：
Mori, F;Nishie, M;Wakabayashi, K
NEDD8（神经前体细胞表达，发育下调 8）是一种类泛素蛋白，通过与 cullin 家族成员结合来控制重要的生物事件，cullin 家族成员是某些泛素 E3 连接酶的组成部分。最近的研究表明，NEDD8 被整合到帕金森病中的路易体 (LB)、酒精性肝病中的马洛里小体以及星形细胞瘤中的罗森塔尔纤维中。为了检查 NEDD8 是否在泛素化包涵体的形成中发挥作用，我们使用不与泛素发生交叉反应的针对 NEDD8 的亲和纯化多克隆抗体，对各种神经退行性疾病患者的脑组织进行了免疫组织化学染色。在 LB 疾病中，几乎所有 LB 和路易神经突中都存在 NEDD8 免疫反应性。此外，NEDD8免疫反应性被发现存在于多种泛素化包涵体中，包括多系统萎缩中的神经元和少突胶质细胞包涵体、阿尔茨海默病中的神经原纤维缠结、运动神经元疾病中的泛素化包涵体以及三重重复疾病中的核内包涵体。这些发现表明 NEDD8 通过泛素-蛋白酶体系统参与各种泛素化包涵体的形成。
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.