We found that inhibition of GSK3 didn’t affect the potassium withdrawal induced up-regulation of downstream JNK targets including P c Jun, P ATF2 and ATF3 implying that JNK signaling isn’t influenced by GSK3b activity. Moreover, JNK downstream targets are not affected by as their induction isn’t affected by AKT activation by IGF 1 order Lenalidomide AKT signaling independently of GSK3b. Finally, we find that GSK3b and AKT phosphorylation levels are not affected by SP600125 mediated JNK inhibition suggesting that JNK is not indirectly modulating the activity of the pathway. Taken together these results suggest that the AKT/GSK3b and JNK paths function independently of the other person during potassium withdrawal in CGNs. The transcription factor FoxO3a is famous to be inactivated via phosphorylation by AKT. More over, FoxO3a is implicated in the regulation of Puma expression in growth factor withdrawal induced apoptosis of lymphoid cells. Consequently, we examined whether FoxO3a is needed for Puma induction in potassium starvation Pyrimidine induced apoptosis of CGNs. . In keeping with the decline in AKT activity we discovered that FoxO3a phosphorylation was reduced in CGNs following potassium deprivation. We transduced CGNs with lentivirus expressing shRNA targeting FoxO3a or a low targeting shRNA being a control, to ascertain whether FoxO3a is required for Puma induction in this paradigm. As demonstrated in Figures 10B and 10C, FoxO3a knock-down resulted in a significant decrease in Puma mRNA induction in response to potassium withdrawal suggesting that FoxO3a contributes to Puma induction in trophic factor deprived CGNs. We next examined whether GSK3b, AKT and JNK Everolimus molecular weight signaling influenced potassium starvation caused FoxO3a dephosphorylation/activation. . Consistent with its power to market AKT activation, IGF 1 suppressed the potassium deprivation induced dephosphorylation of FoxO3a. Interestingly, nevertheless, we discovered that inhibition of either JNK or GSK3 also attenuated potassium deprivation induced FoxO3a dephosphorylation/ activation.. These results suggest that JNK and GSK3b signaling will also be needed for potassium deprivation induced activation even though system remains unclear. In summary, we’ve founded a novel link between kinase pathways and the transcriptional activation of the Bcl 2 family protein Puma that’s critical for the execution of neuronal apoptosis. We propose a model in which the JNK and AKT/ GSK3b pathways are activated independently and meet to regulate transcription facets including FoxO3a that mediate transcriptional induction of Puma which consequently promotes Bax activation and neuronal cell death. Apoptosis has been implicated in the progression of acute and chronic neuro-degenerative situations such as stroke, spinal cord injury, Alzheimers disease, Parkinsons disease and Huntingtons disease. Several kinases have been implicated in the regulation of neuronal apoptosis including JNK, GSK3 and AKT family kinases.