NS 398 and CAY 10404 tend to be more effective and selective COX 2 inhibitors than meloxicam. COX 2 protein has been previously shown to be stated in SH Lonafarnib ic50 cells, and this was confirmed in this study. These results mean that the neural protective effect of meloxicam might be mediated with a system distinctive from COX 2 inhibition. Furthermore, MPP accumulation is shown to develop separately from COX action in rat mesencephalic primary cultured cells. The second interesting finding of the study indicated that meloxicam showed a particular neuroprotective influence against MPP induced toxicity without affecting toxicities induced by other styles of cytotoxic agents. This result strongly implies that meloxicam exerts the effect by functioning on a molecule related to the intracellular signaling cascade mixed up in beginning of MPP toxicity. Rotenone and MPP have a toxicological system similar compared to that of mitochondrial complex I inhibitors, which trigger mitochondrial dysfunction to ultimately go cell death. But, our results suggest that the procedure of MPP to cause mitochondrial dysfunction must be different from that of rotenone. For that reason, the site of action involved in the neuronal defense Retroperitoneal lymph node dissection of meloxicam is almost certainly to be at the upstream signaling stream before the mitochondria in the MPP induced neuronal death. The recently established two professional apoptotic molecules, c Jun N terminal kinase and p38 MAP kinase, are rapidly activated prior to the mitochondrial fall when SH SY5Y cells are confronted with MPP. A JNK service chemical, CEP 1347, suppresses MPTP caused nigral dopaminergic cell death in vivo. Rotenoneinduced neuronal death in SH SY5Y cells can be attenuated by reduction of JNK or p38 pathway. Therefore, meloxicam is unlikely to become a JNK or a p38 MAP kinase inhibitor when exerting its neuroprotective effect. Though our results can not exclude participation of JNK in MPP induced toxicity, It was supported by the present results. On the other hand, the activation of pro survival signaling cascades, PI3K/Akt and MEK/ERK, is demonstrated to rescue cells from MPP toxicity. Taken together, it may be beneficial to examine if the two pro success cascades would account for the Fingolimod supplier neuroprotection of meloxicam. The 3rd significant finding of the study showed that the neuroprotective effect of meloxicam was mediated via the PI3K/Akt signaling pathway. We identified that a PI3K inhibitor, LY294002, canceled the effects of meloxicam against MPP in three independent assays: viz., cell accumulation, DNA fragmentation and Western blot assays, but, it was incorrect for a MEK inhibitor, PD98059.