Silencing of ICERs (Inducible cAMP Early Repressors) results in partial protection of neurons from programmed cell death

CREB (cAMP Responsive Element Binding proteins) together with ATF (Activating Transcription Factor), CREM (cAMP Responsive Element Modulators) and ICER (Inducible cAMP Early Repressor) form a family of transcriptional regulators considered to exert multiple biological functions. In particular, CREB has been shown to play a key role in survival of various cell types, including neurons. ICERs proteins (Inducible cAMP Early Repressors) are the most effective endogenous repressors of CREB.The present study set out a question whether endogenous ICER proteins might be involved in pathways leading to neuronal cell death in vitro.We have used the lentiviral vector (LV), as a vehicle to deliver shRNA, and two well described models of neuronal degeneration (trophic deprivation of cortical neurons and glutamine treatment of dentate gyrus neurons). For both modelswe have found that ICERs’ silencing mildly, although significantly, protects primary cortical neurons from apoptosis.

23 April 2012