NS 398 and CAY 10404 are more effective and selective COX 2 inhibitors than meloxicam. COX 2 protein has been previously proved to be expressed in SH Afatinib ic50 cells, and this was confirmed in this study. These results imply the neural protective effect of meloxicam might be mediated by a procedure distinctive from COX 2 inhibition. In addition, MPP accumulation has been demonstrated to develop independently from COX activity in rat mesencephalic primary cultured cells. The second interesting finding of this study indicated that meloxicam showed a particular neuroprotective impact against MPP induced toxicity without affecting toxicities induced by other forms of cytotoxic agents. This result strongly implies that meloxicam exerts the neuroprotective effect by functioning on a compound related to the intracellular signaling cascade mixed up in beginning of MPP poisoning. Rotenone and MPP have a toxicological system similar compared to that of mitochondrial complex I inhibitors, which trigger mitochondrial dysfunction to ultimately inflict cell death. However, our results suggest that the mechanism of MPP to induce mitochondrial dysfunction should be not the same as that of rotenone. Therefore, the site of action involved in the neuronal protection Immune system of meloxicam is probably to be at the upstream signaling cascade prior to the mitochondria in the MPP induced neuronal death. The recently established two pro apoptotic molecules, p38 MAP kinase and c Jun N terminal kinase, are rapidly activated before the mitochondrial fall when SH SY5Y cells are exposed to MPP. A JNK activation inhibitor, CEP 1347, suppresses MPTP induced nigral dopaminergic cell death in vivo. Rotenoneinduced neuronal death in SH SY5Y cells is also attenuated by genetic reduction of JNK or p38 pathway. Therefore, meloxicam is impossible to work as a JNK or perhaps a p38 MAP kinase inhibitor when applying its neuroprotective effect. This is supported by today’s results, even though our results can not exclude involvement of JNK in MPP induced toxicity. On-the other hand, the activation of pro success signaling cascades, PI3K/Akt and MEK/ERK, is demonstrated to rescue cells from MPP accumulation. Taken together, it may be beneficial to examine if the two professional success cascades could take into account the AP26113 neuroprotection of meloxicam. The next notable finding of the study showed the influence of meloxicam was mediated via the PI3K/Akt signaling pathway. We recognized that the PI3K inhibitor, LY294002, eliminated the neuroprotective effects of meloxicam against MPP in three independent assays: viz., cell poisoning, DNA fragmentation and Western blot assays, however, this was incorrect for a MEK inhibitor, PD98059.