Toxicity of amyloid beta on embryo rat neuronal cells is mediated by tumor necrosis factor related apoptosis inducing ligand

We have previously shown that the expression of TRAIL and its DR5 receptor is significantly increased in human immortalized neuronal cells challenged with amyloid-beta (AB). In order to study possible differences in mechanisms underlying toxicity of either TRAIL and AB in normal neurons, we treated rat embryo cortical and hippocampal cells in primary culture with both substances. Cell viability tests showed that both AB peptide fragments 1-42 and 25-35 significantly reduced cell survival, an effect exerted also by TRAIL in a concentration related manner. The effects of TRAIL appeared stronger in cortical cells than in hippocampal cells. Protein analysis of cells treated with TRAIL revealed an increased expression of the DR4 receptor in cortical cells, whereas increased DR5 receptor expression was found in both cortical and hippocampal cells. On the other hand, the expression of the decoy receptor DcR2 was decreased in both cortical and hippocampal cells. In synthesis, both AB and TRAIL were toxic when incubated with rat embryo cortical or hippocampal neurons in primary culture in vitro. TRAIL toxicity was related to increased levels of TRAIL and its death receptors, as well as to a blunted expression of its decoy neutralizing receptors. Thus, it is plausible to hypothesize that TRAIL has a prominent role in AB-related neuronal death. These findings may represent a rationale for potential novel therapeutic approaches in neurodegenerative disorders.