The precursor form of Brain-Derived Neurotrophic Factor (pro-BDNF) interacts preferentially with the pan-neurotrophin receptor p75 (p75NTR) and vps10p domain-containing receptor sortilin and induces neuronal apoptosis, whereas mature BDNF selectively binds with high affinity to the TrkB kinase receptor and promotes the survival, growth and differentiation of neurons. As proneurotrophins and mature neurotrophins elicit opposite biological effects, Pro-BDNF cleavage in the neuronal system is regulated in a specific and cell-context dependent manner. Pro-BDNF plays important role in negative regulation of neurotrophic actions in the brain.