Abstract
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.
Highlights
Like other growth factors, brain-derived neurotrophic factor (BDNF) is initially synthesized as a precursor composed of 270 amino acid residues
Neurotrophins (NTs), including nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), exert distinct biological actions by binding to their cognate tyrosine kinase receptors (NGF to TrkA, BDNF and NT-4 to tropomyosin receptor kinase B (TrkB), and NT-3 to TrkC), as well as to the low-affinity neurotrophin receptor p75NTR, which belongs to the tumor necrosis factor (TNF) family[1,2,3]
We previously reported that a singlenucleotide polymorphism (SNP) that changes a valine to a methionine at codon 66 (Val66Met) in the pro-region of human BDNF affects memory function as well as the secretion of BDNF19
Summary
Neurotrophins (NTs), including nerve growth factor (NGF), brainderived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), exert distinct biological actions by binding to their cognate tyrosine kinase receptors (NGF to TrkA, BDNF and NT-4 to TrkB, and NT-3 to TrkC), as well as to the low-affinity neurotrophin receptor p75NTR, which belongs to the tumor necrosis factor (TNF) family[1,2,3]. The discovery of NTs and their receptor components has provided new insight into the role of NTs in the formation of neuronal networks during nervous system development and synaptic plasticity, memory formation, learning, and memory in the adult brain[1,3,4,5]. NTs exert long- and short-term actions; long-term trophic actions depend on gene regulation, whereas short-term effects, including chemotrophic effects on developing neurons and synaptic events, are controlled by NTmediated activation of intracellular effectors[5,7]. Since most of the existing literature focuses on the signaling mechanisms and transcriptional/ translational control of NTs, we concentrate on post-translational aspects, in particular the effects of BDNF and its pro-domain (or propeptide) on synaptic plasticity in the brain
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