Molecular mechanisms of cell death mediated by apolipoprotein E receptor family

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The purpose of the research :In former research, the claimants have reported that the apolipoprotein E(ApoE) which is secreted from the astrocytes and the microglias inhibit neuronal cell death through the ApoE receptors which exist in the neuronal cell surface. In the pathway, GSK-3β, which phosphorylates Tau protein, participated. Therefore, in this research, we analyze the difference of the apoptosis suppressing-function and in the intracellular signal transduction pathway by the difference of the ApoE receptor ligand. As the another ApoE receptor ligand, we deal with Reelin, this time.The result :Reelin protected P19 embryonal cells from apoptosis during retinoic-acid induced neuronal differentiation. This increased survival is associated with reelin activation of the phosphatidyl-inositol-3-kinase (PI3K)/Akt pathway. When PI3K was inhibited with LY294002, reelin failed to protect against this retinoic-acid induced apoptosis. The protective effect of reelin includes activating the Src-family kinases/PI3K/Akt pathway which then led to selective phosphorylation of BAD at serine-136, while the phosphorylation-incompetent mutation of BAD (S136A) suppressed this protection.The conclusion :These studies define a novel pathway where reelin binds apoE receptors, significantly activates the PI3K/Akt pathway causing phosphorylation of BAD which helps to protect cells from apoptosing thus serving an important role in promoting the survival of maturing neurons in the brain.