Hints about Huntington's disease

Abstract

Scientists from Johns Hopkins University have defined a mechanism linking abnormal huntingtin protein to neuronal cell death. Mutant huntingtin, with an expanded polyglutamine stretch, interacts with CREB binding protein (CBP), recruits it into cellular aggregates, and prevents it from participating as a co-activator in CREB-mediated transcription. This nuclear depletion and aggregate enrichment of CBP was observed in Huntington's disease (HD) culture and transgenic mice models as well as in human postmortem HD brain tissue. Furthermore, the cell death seen with mutant huntingtin expression in cells grown in culture is decreased following overexpression of CBP, supporting the current hypothesis that the toxic gain-of-function seen with mutant huntingtin involves transcriptional disruption of cell-survival programs. The full paper is published in the March 23 issue of Science. LO