Consistent with their role in protecting from chronic-stress in a variety of cellular contexts, FOXO factors and interactors such as sir-2.1/SIRT1 and ß-catenin also regulate cellular proteotoxicity and neuron survival in models for neurodegenerative diseases such as Huntington's disease (HD) (Morley et al., 2002; Parker et al., 2005, 2012; Burnett et al., 2011) and Alzheimer's disease (AD) (Cohen et al., 2006; Kim et al., 2007). Here, SIRT1 is linked to Huntington disease.