In this study, the beneficial effects of NR in decreasing acetylated‐p53, neuronal apoptosis (both in vitro and in vivo), attenuating microglial activation and overall neuropathology in the LS mouse brain suggests that activation/hyperacetylation of the p53‐mediated apoptotic pathway contributes to the severe encephalopathy observed in LS mice (Figure 8). This evidence concerns the gene TP53 and Encephalopathy.