神経変性疾患の治療展望とトレハロース A Therapeutic Strategy for Neurodegenerative Diorders and Trehalose

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著者

    • 貫名 信行 NUKINA Nobuyuki
    • 理化学研究所脳科学総合研究センター構造神経病理研究チーム Laboratory for Structural Neuropathology, RIKEN Brain Science Institute

抄録

Polyglutamine diseases, such as Huntington disease (HD) and spinocerebellar ataxia 1 and 3, are autosomal dominant neurodegenerative disorders. They are caused by CAG trinucleotide repeat expansions that are translated into abnormally long polyglutamine tracts. One of the pathological hallmarks in polyglutamine diseases is the formation of intranuclear inclusions of polyglutamine-containing proteins in the brain. We developed a novel in vitro model system for polyglutamine diseases using myoglobin as a host protein. We searched for small molecules that inhibit polyglutamine-mediated aggregation by in vitro screening with a mutant myoglobin containing a 35 polyglutamine repeat. The screening assay revealed that disaccharides have a potential to inhibit polyglutamine-induced protein aggregation and to increase survival in a cellular model of HD. Oral administration of trehalose, the most effective disaccharide in vitro, decreased polyglutamine aggregates in the cerebrum and liver, improved motor dysfunction and extended life span in a transgenic mouse model of HD. In vitro experiments suggest that the beneficial effects of trehalose result from its ability to bind and stabilize polyglutamine-containing proteins. The lack of toxicity and high solubility, coupled with its efficacy upon oral administration, make trehalose promising as a therapeutic drug or lead compound for the treatment of polyglutamine diseases.

収録刊行物

  • 低温生物工学会誌 = Cryobiology and cryotechnology

    低温生物工学会誌 = Cryobiology and cryotechnology 52(1), 25-29, 2006-06-30

    低温生物工学会

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各種コード

  • NII論文ID(NAID)
    110006783012
  • NII書誌ID(NCID)
    AN10448734
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    13407902
  • NDL 記事登録ID
    8077281
  • NDL 雑誌分類
    ZP1(科学技術--化学・化学工業) // ZR2(科学技術--生物学--生化学)
  • NDL 請求記号
    Z17-945
  • データ提供元
    CJP書誌  NDL  NII-ELS 
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