Neuroprotection Signaling of Nuclear Akt in Neuronal Cells

Akt is one of the central kinases that perform a pivotal function in mediating survival signaling in a wide range of neuronal cell types in response to growth factor stimulation. The recent findings of a number of targets for Akt suggest that it prohibits neuronal death by both impinging on the cytoplasmic cell death machinery and by regulating nuclear proteins. The presence of active Akt in the nuclei of mammalian cells is no longer debatable, and this has been corroborated by the finding of multiple targets in the nucleus of PC12 cells. However, it is also clear that the nuclear Akt signaling exists independent of the cytosolic Akt signaling, thereby showing a distinctive feature of nuclear Akt signaling as opposed to its cytosolic counterpart. The principal objective of this review is to summarize our current state of knowledge regarding nuclear Akt signaling in neuronal survival, and to introduce current theories regarding the roles of nuclear Akt in neuron.