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Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch

Nature Genetics volume 18, pages 111–117 (1998)Cite this article

Abstract

To elucidate the molecular mechanisms whereby expanded polyglutamine stretches elicit a gain of toxic function, we expressed full-length and truncated DRPLA (dentatorubral-pallidoluysian atrophy) cDNAs with or without expanded CAG repeats in COS-7 cells. We found that truncated DRPLA proteins containing an expanded polyglutamine stretch form filamentous peri- and intranuclear aggregates and undergo apoptosis. The apoptotic cell death was partially suppressed by the transglutaminase inhibitors cystamine and monodansyl cadaverine (but not putrescine), suggesting involvement of a transglutaminase reaction and providing a potential basis for the development of therapeutic measures for CAG-repeat expansion diseases.

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Authors and Affiliations

  1. Departments of Neurology, Brain Research Institute, Niigata University, 1-757, Asahimachi Niigata, 951, Japan

    Shuichi Igarashi, Reiji Koide, Takayoshi Shimohata, Yasuko Hayashi, Hiroki Takano, Hidetoshi Date, Mutsuo Oyake, Toshiya Sato, Aki Sato, Takeshi Ikeuchi, Hajime Tanaka, Ryoichi Nakano, Keiko Tanaka, Isao Hozumi, Takashi Inuzuka & Shoji Tsuji

  2. Departments of Pathology, Brain Research Institute, Niigata University, 1-757, Asahimachi Niigata, 951, Japan

    Mitsunori Yamada, Yasuko Hayashi, Shigekimi Egawa & Hitoshi Takahashi

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Correspondence to Shoji Tsuji.

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Igarashi, S., Koide, R., Shimohata, T. et al. Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch. Nat Genet 18, 111–117 (1998). https://doi.org/10.1038/ng0298-111

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