CREB1 and epilepsy: CREB upregulation boosts the transcription of its target genes, which results in the enhancement of mossy fiber sprouting and an increase in the number of dysfunctional synapses in neural circuits, resulting in poor AED treatment outcomes for patients with epilepsy and ultimately developing into refractory epilepsy (Redmond et al., 2002; Finsterwald et al., 2010).