cAMP-PKA-CREB-BDNF signaling pathway

The cAMP–PKA–CREB–BDNF signaling pathway is an intracellular cascade that mediates the effects of extracellular signals (usually through G protein-coupled receptors activating adenylyl cyclase) on gene transcription and neural plasticity. cAMP acts as a second messenger to activate PKA, which translocates to the nucleus and phosphorylates CREB at Ser133. Phosphorylated CREB binds DNA at cAMP response elements, promoting the transcription of genes including BDNF. This sequence underlies key processes such as synaptic plasticity, learning, memory, neurogenesis, and cell survival. Disruption of this pathway is implicated in depression, cognitive impairment, neurodegeneration, and, in some contexts, cancer. Note: For molecular target databases or drug discovery purposes, it is more appropriate to query, annotate, and drug individual pathway components (such as "cAMP-dependent protein kinase catalytic subunit alpha", "cAMP response element-binding protein", or "brain-derived neurotrophic factor") rather than the composite pathway name.

Other names

cAMP/PKA/CREB/BDNF signaling pathwaycAMP–PKA–CREB–BDNF axiscAMP-responsive signaling pathway

Increase cAMP levels, leading to PKA activation (e.g., PDE inhibitors). Activate PKA, resulting in CREB phosphorylation and BDNF upregulation (targeting memory and mood disorders). Modulate CREB activity to increase or decrease BDNF expression. Modulate synaptic plasticity, neuroprotection, and neurogenesis.