Information in combination show that NAD levels are raised through increasing PBEF enzymatic reaction by giving substrate. Consistent with this concept, the savings of NAD levels caused by OGD were improved via management of NAM in a time dependent fashion. Neuronal death on account of NAD depletion also requires ATP shortage leading to cellular energy depletion. In preserving depletion of NAD, OGD also triggered p53 ubiquitination an important reduction of ATP, while NAD replenishment maintained intracellular ATP content at almost normal levels, suggesting the maintenance of mobile energy homeostasis and NAD levels is of crucial importance in helping the neuronal survival. Curiously, both NAM and NAD can increase ATP content if you have not any excitement. We reasoned that NAM management may increase NAD resynthesis by PBEF as the enzymatic reaction rate is increased with the high substrate concentration, and this mediation of NAD is a effective and indirect means of saving power failure. NAD is recognized as a vital energy substrate and cofactor involved in multiple metabolic reactions, including glycolysis, DNA repair processes, and the function of several NAD dependent enzymes, like the poly polymerase 1 and histodeacetylase Organism SIRT1. In ischemic problem, those NAD consuming enzymes might have harmful effect on neuronal viability through the depletion of NAD and ATP pool. Our previous study showed that PBEF knockout mice have a lowered amount of NAD as compared with WT mice, therefore it is going to be important to test whether the neuronal protective influence in ischemia in vivo by the overexpression of PBEF is through the regulation of the activities and expression levels of PARP 1 and SIRT1. Transgenic mice or viral transduction that can effortlessly overexpress PBEF in neurons in vivo are required for all those reports, since DNA transfection in principal neuronal culture has very low efficiency. Mitochondrial oxidative phosphorylation may be the main supply of high energy compounds in the cell. Disorder of mitochondrial energy metabolic process leads to impaired deubiquitination assay calcium loading and generation of ROS. Further, disadvantaged mitochondria also may minimize ATP production, thereby impairing the synthesis and secretion of neurotransmitters that serve as signs in CNS. Since PBEF is just a rate limiting enzyme that digests NAD, we postulate it will reduce mitochondrial bioenergetic failure after ischemia. Using MitoTracker, we found NAM and NAD may also avoid OGD induced mitochondrial damage which is also confirmed by measuring the nucDNA and mtDNA. The results indicate PBEF is critical in maintaining mitochondrial homeostasis and biogenesis, for that reason neuronal viability in health and infection. Our effects corroborated with the report that extended focal cerebral ischemia causes permanent loss of mtDNA, an indication of the failure of mitochondrial repair mechanisms.