Figure 10.

Schematic presentation of the summary of our work. Fibrillar Aβ alone is capable of activating the N-SMase–ceramide pathway in neurons, which leads to apoptosis and cell death (Jana and Pahan, 2004a,b). In astroglia, fibrillar Aβ-mediated activation of the N-SMase–ceramide pathway is responsible for the activation of NF-κB and the expression of different proinflammatory soluble mediators including NO. Once NO is produced, it can induce the expression of GFAP in astrocytes leading to astrogliosis. On the other hand, these glial-derived soluble mediators (e.g., NO) also induce neuronal apoptosis via the N-SMase–ceramide pathway. It appears that multiple neurotoxic signaling pathways converge on N-SMase. SM, Sphingomyelin.