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Immunohistochemical localization of NUB1, a synphilin-1-binding protein, in neurodegenerative disorders

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Abstract

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 α-synucleinopathy lesions. However, yeast two-hybrid assay demonstrated that NUB1 did not directly interact with α-synuclein.

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Acknowledgments

This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (to K.W.), a grant from the Research Committee on Neurodegenerative Diseases, Ministry of Health, Labor and Welfare, Japan (to H.T.), the Karoji Memorial Fund for Medical Research (to K.T.), and a Fund for the Promotion of International Scientific Research from Hirosaki University (to K.T.), and National Institutes of Health Grant R01 AG024497 (to T.K.). The authors wish to express their gratitude to M. Nakata for her technical assistance.

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Authors and Affiliations

  1. Department of Neuropathology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki, 036-8562, Japan

    Kunikazu Tanji, Fumiaki Mori, Haixin Zhang & Koichi Wakabayashi

  2. Department of Pathological Neuroscience, Center for Bioresource-based Researches, Brain Research Institute, University of Niigata, Niigata, Japan

    Akiyoshi Kakita

  3. First Department of Pathology, Ehime University School of Medicine, Ehime, Japan

    Katsumi Kito

  4. Department of Cardiology, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Tetsu Kamitani

  5. Department of Pathology, Brain Research Institute, University of Niigata, Niigata, Japan

    Hitoshi Takahashi

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  1. Kunikazu Tanji
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Correspondence to Kunikazu Tanji.

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Tanji, K., Mori, F., Kakita, A. et al. Immunohistochemical localization of NUB1, a synphilin-1-binding protein, in neurodegenerative disorders. Acta Neuropathol 114, 365–371 (2007). https://doi.org/10.1007/s00401-007-0238-1

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