Figure 1.

BDNF molecular mechanisms and signaling cascades. The BDNF protein is synthesized as a precursor form, preproBDNF. PreproBDNF is then converted into proBDNF, which consists of a pro-domain and a mature domain. The proBDNF is further cleaved to generate the mature isoform, mBDNF. ProBDNF and mBDNF are exocytosed into the extracellular space. The pro-domain of the proBDNF binds to the sortilin receptor, while the mature domain binds to the p75NTR receptor and activates the JNK/cJUN, PI3K/AKT, and TRAF6/NF-kB signaling pathways, which determine neuronal fate. The mBDNF binds to the TrkB receptor and activates PLCs, PI3K, MAPK, and JAK/STAT signaling cascades, which promote CREB translation, neuronal survival, and synaptic plasticity.