Differences in the Biological Functions of BDNF and proBDNF in the Central Nervous System

Brain-derived neurotrophic factor (BDNF) is one of the most widely distributed protein regulators of many biological processes in the central nervous system. Like other neurotrophins, BDNF is synthesized in cells as a precursor molecule (proBDNF), which undergoes proteolytic cleavage to form the mature form, BDNF. The effectiveness of proteolysis of the proform and, thus, the proBDNF/BDNF ratio, has been shown to be determined by the nature of concomitant neuronal activity. Extensive data have provided evidence that the BDNF precursor (proBDNF) has intrinsic biological functions, which are often diametrically opposed to the functions of the mature neurotrophin. Thus, the proBDNF/BDNF balance is an important component in the regulation of many process in central nervous system cells. This review considers the key points in BDNF expression and its proteolysis to BDNF, as well as the role of brain-derived neurotrophic factor in the developing nervous system, in the processes of long-term synaptic plasticity, memory consolidation and extinction, and possible involvement in the development of various nervous system pathologies.