Figure 11

Figure A: Possible anti-oxidant mechanisms involved in the LPS, Aβ-induced ceramide generation leading to superoxide anion formation, nitric oxide release and peroxynitrite generation. Figure B: inflammation is possibly triggered as a result of imbalance in the radical generating systems and radical scavenger systems creating an oxidative stress, thus leading to the formation of nitric oxide and superoxide anion generation, and thereby depleting cellular anti-oxidants. Figure C. Putative role of ceramide in eicosanoid synthesis. Ceramide generated as a result of LPS- and Aβ-peptide induced SMase activation, leads to the release of eicosanoids. Eicosanoids (leukotrienes and prostaglandins) thus generated may perhaps potentially enhance or ameliorate the cytokine-induced pro-inflammatory responses or vice versa. Non steroidal anti-inflammatory drugs (NSAIDs) as well as COX inhibitors block these responses. Figure D. Overall scheme in the LPS, Aβ-induced pro-inflammatory signaling cascade involving cytokine release thereby leading to the expression of iNOS, COX-2 and MnSOD. The anti-inflammatory effect of AICAR is perhaps a result of its multiple regulatory roles. However, AICAR blockade of ROS generation keeps the redox balance in check, thereby inhibiting the inflammatory signaling cascade.