Remedy for CAG repeat expansion diseases

摘要

To elucidate the molecular mechanisms of gain of toxic function of expanded polyglutamine stretches in CAG repeat expansion diseases, the inventors established an expression system of full-length and truncated cDNAs for dentatorubral-pallidoluysian atrophy (DRPLA) and found that truncated DRPLA proteins containing the expanded polyglutamine stretch, but not the full-length protein, form peri- and intra-nuclear aggregates consisting of filaments and concomitant apoptosis. The apoptotic cell death was partially suppressed by transglutaminase inhibitors, cystamine and monodansyl cadaverine, raising the possibility of involvement of transglutaminase reaction. The results may provide a potential basis for the development of therapeutic measures for CAG repeat expansion diseases.