SUPPRESSION OF AGGREGATE FORMATION AND APOPTOSIS BY TRANSGLUTAMINASE INHIBITORS IN CELLS EXPRESSING TRUNCATED DRPLA PROTEIN WITH AN EXPANDED POLYGLUTAMINE STRETCH

To elucidate the molecular mechanisms whereby expanded polyglutamine s tretches 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 D RPLA proteins containing an expanded polyglutamine stretch form filame ntous peri-and intranuclear aggregates and undergo apoptosis. The apop totic cell death was partially suppressed by the transglutaminase inhi bitors cystamine and monodansyl cadaverine (but not putrescine), sugge sting involvement of a transglutaminase reaction and providing a poten tial basis for the development of therapeutic measures for GAG-repeat expansion diseases.