Tanji Kunikazu, Mori Fumiaki, Kakita Akiyoshi, Zhang Haixin, Kito Katsumi, Kamitani Tetsu, Takahashi Hitoshi, Wakabayashi Koichi
Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Acta Neuropathol. 2007 Oct;114(4):365-71. doi: 10.1007/s00401-007-0238-1. Epub 2007 Jun 5.
Recently, we showed that NUB1 is a synphilin-1-interacting protein and that NUB1, as well as synphilin-1, accumulates in Lewy bodies in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and glial cytoplasmic inclusions in multiple system atrophy (MSA). In this study, an investigation was further conducted to elucidate the immunohistochemical localization of NUB1 in various neurodegenerative disorders. In controls, anti-NUB1 antibody weakly immunolabeled neuronal perikarya. In PD and DLB, cortical and brainstem-type Lewy bodies, pale bodies and Lewy neurites were strongly immunolabeled with anti-NUB1. In MSA, NUB1 immunoreactivity was found in the intracytoplasmic inclusions of both neuronal and oligodendroglial cells, neuronal nuclear inclusions, and swollen neurites. No NUB1 immunoreactivity was found in a variety of other neuronal or glial inclusions in other disorders, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degeneration, motor neuron disease and triplet-repeat diseases. These findings indicate that the abnormal accumulation of NUB1 is specific for alpha-synucleinopathy lesions. However, yeast two-hybrid assay demonstrated that NUB1 did not directly interact with alpha-synuclein.
最近，我们发现NUB1是一种与突触核蛋白-1相互作用的蛋白，并且NUB1以及突触核蛋白-1在帕金森病（PD）和路易体痴呆（DLB）的路易小体中积聚，在多系统萎缩（MSA）的胶质细胞胞质内包涵体中也有积聚。在本研究中，我们进一步开展调查以阐明NUB1在各种神经退行性疾病中的免疫组织化学定位。在对照组中，抗NUB1抗体对神经元胞体进行弱免疫标记。在PD和DLB中，皮质和脑干型路易小体、苍白小体和路易神经突被抗NUB1强烈免疫标记。在MSA中，在神经元和少突胶质细胞的胞质内包涵体、神经元核内包涵体以及肿胀的神经突中发现了NUB1免疫反应性。在包括阿尔茨海默病、匹克病、进行性核上性麻痹、皮质基底节变性、运动神经元病和三核苷酸重复疾病在内的其他疾病的各种神经元或胶质细胞包涵体中未发现NUB1免疫反应性。这些发现表明NUB1的异常积聚对α-突触核蛋白病病变具有特异性。然而，酵母双杂交试验表明NUB1并不直接与α-突触核蛋白相互作用。
