For instance, FOXO3a and its Caenorhabditis elegans homologue daf-16 have been shown to at least partially mediate the protective effect of sirtuins SIRT1 or sir-2.1 against mutant HTT toxicity in Hdh111/111 cells or in a nematode HD model, respectively (39, 66). Here, SIRT1 is linked to Huntington disease.