Another study indicated that SIRT6 levels affect synaptic plasticity and neuronal survival via regulating Akt-GSK3β signaling, moreover, upregulated SIRT6 is related to depression-like behavior, which indicated that SIRT6 might exert neurotoxic effect on neuron (Mao et al., 2017) Another study on PD suggest that SIRT6 plays a pathogenic and pro-inflammatory role (Nicholatos et al., 2018). Here, SIRT6 is linked to major depressive disorder.