BDNF and major depressive disorder: Mechanistically, BDNF exerts neuroprotective effects through the Mitogen-activated protein kinase kinase/B-cell lymphoma 2 (MEK/Bcl2) signaling pathway [85], while cAMP response element-binding protein (CREB), as a downstream transcription factor of the BDNF pathway, is associated with reduced activity in the occurrence of depression [86].