Mutant Huntingtin Expression in Clonal Striatal Cells: Dissociation of Inclusion Formation and Neuronal Survival by Caspase Inhibition

摘要: Neuronal intranuclear inclusions are found in the brains of patients with Huntington’s disease and form from polyglutamine-expanded N-terminal region mutant huntingtin. To explore properties their involvement cell death, mouse clonal striatal cells were transiently transfected truncated full-length human wild-type huntingtin cDNAs. Both normal proteins localized cytoplasm, infrequently, dispersed perinuclear vacuoles. Only formed nuclear cytoplasmic inclusions, which increased polyglutamine expansion time after transfection. Nuclear contained primarily cleaved products, whereas larger intact proteins. Cells or protein had distinct apoptotic features (membrane blebbing, shrinkage, cellular fragmentation), but those generated most fragments (apoptotic bodies). The caspase inhibitor Z-VAD-FMK significantly survival did not diminish inclusions. In contrast, Z-DEVD-FMK reduced increase survival. A series products was One prominent product blocked by Z-VAD-FMK. summary, formation corresponds to that seen HD brain is separable events regulate death. cleavage may be linked huntingtin’s role