Oxidative stress influences neuronal cell survival and homeostasis,but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated.We have shown that protein kinase Hippo/MST1 plays a major role in oxidative stress-induced cell death in primary mammalian neurons and the protein kinase c-Abl phosphorylates MST1 at Y433,which triggers the stabilization and activation of MST1,thereby activating the MST1-FOXO signaling pathway,leading to cell death in both primary culture neurons and rat hippocampal neurons.Microglial activation has been implicated as a secondary and detrimental cellular response for neuronal cell death in neurodegenerative diseases.Recently we found that MST1 is also involved in the microglial activation through directly phosphorylating IκB as to initiate the immune response.We further identified that Src kinase functions as the upstream of MST1-IκB signaling during microglial activation.Taken together,we demonstrated that Hippo/MST signaling plays a critical role in both neuronal cell death and microglial activation upon oxidative stress,with the implication of a therapeutic target for the neurodegenerative diseases.