proBDNF (the precursor form of Brain-derived neurotrophic factor) interacts preferentially with p75NTR (the pan-neurotrophin receptor p75) and vps10p domain-containing receptor sortilin and induces neuronal apoptosis,while the mature BDNF selectively binds with great affinity to the TrkB kinase receptor and promotes the survival,growth and differentiation of neurons. Since proneurotrophins and mature neurotrophins bring forth opposite biological effects,proBDNF cleavage in the neuronal system is regulated in a specific and cell-context dependent manner. proBDNF has an important role in negative regulation of neurotrophic actions in the brain.