Nurr1 Protein Is Required for N-Methyl-d-aspartic Acid (NMDA) Receptor-mediated Neuronal Survival

Abstract

Background:The mechanism involved in activity-dependent survival of neurons in the central nervous system is not fully understood. Results: Nurr1 is involved in excitatory transmission-dependent survival of glutamatergic neurons by acting downstream CREB and upstream of BDNF. Conclusion: Nurr1 activation mediates activity-dependent survival of glutamatergic neurons. Significance: A novel function of Nurr1 in activity-dependent survival of glutamatergic neurons is reported.

Ras Protein Activation Is a Key Event in Activity-dependent Survival of Cerebellar Granule Neurons

“…A possibility could be a differential effect downstream ERK. One of the main cytosolic ERK substrates is p90Rsk that directly phosphorylates the cAMP-response element-binding protein (CREB), perhaps the most important transcription factor related to activity-dependent neuronal survival in general and for CGNs survival in particular (30,39). However, we have observed that both NMDA and K25 are able to activate p90Rsk and CREB (Ref.…”

“…The involvement of this pathway in NMDA-mediated survival of CGNs was also reported previously in immature CGNs at 4 DIV (12). It has also been described that BDNF release mediates NMDA pro-survival effect on CGNs (26,30,36,37) and BDNF also promote CGNs survival through activation of PI3K/Akt (13). Thus it is likely that, although NMDA receptor stimulation could activate this pathway directly (35), NMDA-mediated activation of Akt is due to BDNF-mediated stimulation of its receptor.…”

The Role of Histone Acetylation in Memory Formation and Cognitive Impairments

“…On the other hand, CREB target genes Nr4a1 and Nr4a2 expression as well as promoter acetylation are selectively increased after TSA inhibition (Vecsey et al, 2007). Interestingly, Nr4a2 binds to Bdnf promoter 4, and silencing Nr4a2 by shRNA leads to a decrease in BDNF protein levels and a reduction of the effect of NMDA in neuronal survival (Barneda-Zahonero et al, 2012). CREBdependent neuroprotection has also been shown to be mediated by NR4A orphan receptors (Volakakis et al, 2010).The Creb promoter itself changes acetylation status after learning.…”

Involvement of the GluN2A and GluN2B Subunits in Synaptic and Extrasynaptic N-methyl-d-aspartate Receptor Function and Neuronal Excitotoxicity

“…Cascade-Numerous studies have demonstrated that appropriate activation of NMDAR activates prosurvival molecules (such as CREB) and supports neuronal survival (17,(25)(26)(27). NMDAR overactivation results in significant cell death.…”