Fig. 3.
Gene expression and metabolic effects of SIRT2 inhibition in neurons. (A) Multiple genes controlling sterol biosynthesis are down-regulated by AK-1 treatment. Scheme depicts enzymes in sterol biosynthesis whose RNAs are down-regulated by AK-1 treatment by the criterion of FDR P < 0.05. (The segment of the pathway between acetoacetate and cholesterol is shown.) Full analyses of the data, including statistical measures, fold-changes, and Gene Ontology analyses, are presented in Dataset S1 and S2. (B–D) SIRT2 inhibition reverses Htt171-82Q-mediated increase in sterols. (B) DMSO-treated neurons expressing Htt171-82Q had significantly higher sterol levels (cholesterol and cholesteryl esters) than those expressing either CFP or Htt171-18Q and this effect was reversed by treatment with AK-1, AGK2 (5 μM, 48 hrs) (C), and SIRT2H150Y (D) (*P < 0.05).