Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch - PubMed (original) (raw)

R Koide, T Shimohata, M Yamada, Y Hayashi, H Takano, H Date, M Oyake, T Sato, A Sato, S Egawa, T Ikeuchi, H Tanaka, R Nakano, K Tanaka, I Hozumi, T Inuzuka, H Takahashi, S Tsuji

Affiliations

PMID: 9462738
DOI: 10.1038/ng0298-111

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

S Igarashi et al. Nat Genet. 1998 Feb.

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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Suppression of aggregate formation and apoptosis by transglutaminase inhibitors in cells expressing truncated DRPLA protein with an expanded polyglutamine stretch - PubMed (original) (raw)