Transcriptional control of nerve cell death, survival and repair

Abstract

15. Conclusions: The data reviewed here demonstrate the paradoxical involvement of the bZIP transcription factors in the mechanisms mediating nerve cell death as well as those promoting survival and repair after injury. Precisely, how these transcription factors regulate such diverse cellular processes awaits clarification but differential phosphorylation and dimer partner availability are likely to be key factors. For example, c-Jun-mediated regeneration is associated with selective phosphorylation of Ser73 and dimerization with ATF-3, whereas Ser63 phosphorylation and dimerization with ATF-2 can (at least in some cases) result in c-Jun-mediated cell death. Similarly, the duration of CREB phosphorylation appears to be related to its function, since prolonged phosphorylation is associated with neuroprotection, whereas dephosphorylation is associated with neurotoxicity. Whether these observations represent fundamental conserved responses to injury or are dependent on the insult and cell-type remains to be determined. However, these transcription factors and the signaling mechanisms they control represent potential targets for the design of new therapies to prevent nerve cell death and promote survival and repair after injury.