[Show abstract][Hide abstract] ABSTRACT: We report that Sir2 activation through increased sir-2.1 dosage or treatment with the sirtuin activator resveratrol specifically rescued early neuronal dysfunction phenotypes induced by mutant polyglutamines in transgenic Caenorhabditis elegans. These effects are dependent on daf-16 (Forkhead). Additionally, resveratrol rescued mutant polyglutamine-specific cell death in neuronal cells derived from HdhQ111 knock-in mice. We conclude that Sir2 activation may protect against mutant polyglutamines.
[Show abstract][Hide abstract] ABSTRACT: The identification of disease genes for several neurodegenerative illnesses has allowed for the development of disease models in experimental organisms. We discuss our approach to studying Huntington's disease, the best characterized of the polyglutamine (polyQ) expansion disorders. We have developed a system in Caenorhabditis elegans to study the effects of (polyQ)-dependent neuronal dysfunction at the resolution of two neurons in screening for genetic and pharmacological suppression. Our data suggest that C. elegans might be instructive in searching for targets and active compounds against polyglutamine neuronal toxicity.