SIRT1 and Alzheimer disease: In addition to increasing sCLU (Supplementary Fig. S9A), treatment of SH-SY5Y cells with DDL-357 at a concentration of 200 nM significantly increased expression of the master metabolic regulator sirtuin 1 (SirT1) and mitochondrial-derived peptide humanin (HN) (Fig. 6B, C, respectively; Supplementary Fig. S9B, and C), both of which have numerous neuroprotective functions shown to lessen AD pathology and improve cognition45–47.