GSK3β Controls mTOR and Prosurvival Signaling in Neurons

Glycogen synthase kinases-3 beta (GSK3 beta) is a key regulator of cell homeostasis. In neurons, GSK3 beta contributes to control of neuronal transmission and plasticity. Despite extensive studies in non-neuronal cells, crosstalk between GSK3 beta and other signaling pathways remains not well defined in neurons. In the present study, we report that GSK3 beta positively affected the activity of effectors of mammalian target of rapamycin complex 1 (mTORC1) and complex 2 (mTORC2), in mature neurons in vitro and in vivo. GSK3 beta also promoted prosurvival signaling and attenuated kainic acid-induced apoptosis. Our study identified GSK3 beta as a positive regulator of prosurvival signaling, including the mTOR pathway, and indicates the possible neuroprotective role of GSK3 beta in models of pharmacologically induced excitotoxicity.