α7 Nicotinic receptor activation reduces β‐amyloid‐induced apoptosis by inhibiting caspase‐independent death through phosphatidylinositol 3‐kinase signaling

摘要: J. Neurochem. (2011) 119, 848–858. Abstract The neurotoxicity of amyloid-β (Aβ) involves caspase-dependent and -independent programmed cell death. The latter is mediated by the nuclear translocation mitochondrial flavoprotein apoptosis inducing factor (AIF). Nicotine has been shown to decrease Aβ via inhibition apoptosis, but it unknown if its neuroprotection through caspase-independent pathways. In present study, pre-treatment with nicotine in rat cortical neuronal culture markedly reduced Aβ1–42 induced This effect was accompanied a significant reduction AIF release subsequent as well cytochrome c caspase 3 activation. Pre-treatment selective α7nicotinic acetylcholine receptor(nAChR) antagonist (methyllycaconitine), not α4 nAChR (dihydro-β-erythroidine), could prevent neuroprotective on release/translocation, suggesting that inhibits death pathway α7 nAChR-dependent fashion. Furthermore, action release/translocation suppressed LY294002, phosphatidylinositol 3-kinase (PI3K) inhibitor. significantly restored Akt phosphorylation, an effector PI3K, Aβ1–42-treated neurons. These findings indicate activation PI3K/Akt transduction signaling contribute effects against Aβ-induced modulating