Recent Advances in the Biology of BDNF And the Newly Identified Pro-Peptide

Most growth factors are initially synthesized as precursors. To produce biologically active mature peptides, the pro-domain is cleaved by proteolytic processing. However, compared with mature bioactive growth factors, the biological roles of pro-domains are poorly understood. Recent new findings on brain-derived neurotrophic factor (BDNF), a growth factor in the brain that promotes neuronal survival, differentiation, and synaptic plasticity, have been reported. Interestingly, the pro-domain (pro-peptide) of BDNF is endogenously present and localized at presynaptic termini, where it surprisingly functions as a facilitator of long-term depression (LTD). Given that BDNF elicits synaptic transmission and long-term potentiation (LTP), BDNF and its pro-peptide might exert distinct roles in synaptic plasticity in the central nervous system (CNS). In addition to reports on the BDNF pro-peptide, we review recent literature on the role of BDNF in the peripheral nervous system (PNS), and in brain-body interactions following exercise. Together, these findings provide new insight into BDNF biology.