Chemical chaperone therapy for brain pathology in G <sub>M1</sub> -gangliosidosis
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- Junichiro Matsuda
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Osamu Suzuki
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Akihiro Oshima
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Yoshie Yamamoto
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Akira Noguchi
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Kazuhiro Takimoto
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Masayuki Itoh
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Yuji Matsuzaki
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Yosuke Yasuda
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Seiichiro Ogawa
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Yuko Sakata
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Eiji Nanba
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Katsumi Higaki
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Yoshimi Ogawa
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Lika Tominaga
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Kousaku Ohno
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Hiroyuki Iwasaki
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Hiroshi Watanabe
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Roscoe O. Brady
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
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- Yoshiyuki Suzuki
- Department of Veterinary Science, and Division of Experimental Animal Research, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan; Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan; Central Research Laboratories, Seikagaku Corporation, 3-1253 Tateno, Higashi-Yamato, Tokyo 207-0021, Japan; Department of Biosciences...
抄録
<jats:p> We synthesized a galactose derivative, <jats:italic>N-</jats:italic> octyl-4-epi-β-valienamine (NOEV), for a molecular therapy (chemical chaperone therapy) of a human neurogenetic disease, β-galactosidosis (G <jats:sub>M1</jats:sub> -gangliosidosis and Morquio B disease). It is a potent inhibitor of lysosomal β-galactosidase <jats:italic>in vitro</jats:italic> . Addition of NOEV in the culture medium restored mutant enzyme activity in cultured human or murine fibroblasts at low intracellular concentrations, resulting in a marked decrease of intracellular substrate storage. Short-term oral administration of NOEV to a model mouse of juvenile G <jats:sub>M1</jats:sub> -gangliosidosis, expressing a mutant enzyme protein R201C, resulted in significant enhancement of the enzyme activity in the brain and other tissues. Immunohistochemical stain revealed a decrease in the amount of G <jats:sub>M1</jats:sub> and G <jats:sub>A1</jats:sub> in neuronal cells in the fronto-temporal cerebral cortex and brainstem. However, mass biochemical analysis did not show the substrate reduction observed histochemically in these limited areas in the brain probably because of the brief duration of this investigation. Chemical chaperone therapy may be useful for certain patients with β-galactosidosis and potentially other lysosomal storage diseases with central nervous system involvement. </jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 100 (26), 15912-15917, 2003-12-15
Proceedings of the National Academy of Sciences
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詳細情報
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- CRID
- 1364233270344072448
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- NII論文ID
- 80016487198
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- ISSN
- 10916490
- 00278424
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