Biochemical characterization of sirtuin 6 in the brain and its involvement in oxidative stress response

Sirtuin 6 (SIRT6) is a member of nicotinamide adenine dinucleotide-dependent deacetylase protein family and has been implicated in the control of glucose and lipid metabolism, cancer, genomic stability and DNA repair. Moreover, SIRT6 regulates the expression of a large number of genes involved in stress response and aging. The role of SIRT6 in brain function and neuronal survival is largely unknown. Here, we biochemically characterized SIRT6 in brain tissues and primary neuronal cultures and found that it is highly expressed in cortical and hippocampal regions and enriched in the synaptosomal membrane fraction. Immunoblotting analysis on cortical and hippocampal neurons showed that SIRT6 is downregulated during maturation in vitro, reaching the lowest expression at 11 days in vitro. In addition, SIRT6 overexpression in terminally differentiated cortical and hippocampal neurons, mediated by a neuron-specific recombinant adeno-associated virus, downregulated cell viability under oxidative stress condition. By contrast, under control condition, SIRT6 overexpression had no detrimental effect. Overall these results suggest that SIRT6 may play a role in synaptic function and neuronal maturation and it may be implicated in the regulation of neuronal survival.