SIRT1 and Huntington disease: SIRT1 expression is increased in HD-affected brain regions, and metabolic pathways are altered in the hypothalamus of individuals with HD.768 An important finding is that the manipulation of sterol biosynthesis at the transcriptional level mimics SIRT2 inhibition, which demonstrates that the metabolic effects of SIRT2 inhibition are sufficient to diminish mutant huntingtin toxicity.769 This study demonstrated that inhibition of SIRT2 achieves neuroprotection in cellular and invertebrate models of HD.