In addition, other possibilities may account for the differential effects of modulating SIRT2: i) a compensatory effect leading to increased SIRT1 expression, as shown in our study [2], a non-negligible phenomenon not explored in the AD and PD models described; or ii) a direct impact on the limited pool of NAD+, a main metabolic regulator linking cellular metabolism to changes in signaling and transcriptional events, through redox enzymatic reactions or through NAD+-consuming enzymes such as sirtuins or PARP-1, among others [7]. This evidence concerns the gene SIRT2 and Alzheimer disease.