activities in neuronal cell cultures, suggesting that both SMases might collaborate and contribute to Aβ signaling. Taken together, these data strongly suggest that N-SMase activation, likely the nSMase2 isoform, contributes at least partially to Aβ cytotoxicity and may be a potential therapeutic target for AD in the future. However, it should also be noted that all three cloned nSMases as well as acid SMase have all been detected in the central nervous system, therefore making it a complex task to elucidate the relative contribution of each SMase. Nevertheless, these data suggest that the various SMase isoforms should be the subject of active investigation relating to the pathogenesis of neuronal disorders.
