BDNF pro-peptide：a novel synaptic modulator generated as an N-terminal fragment from the BDNF precursor by proteolytic processing

Most growth factors are initially synthesized as precursors and it was cleaved into bioactive mature domain and pro-domain.However,compared with the expression and function of bioactive mature domain,the biological role of the pro-domain is poorly understood.Unexpectedly,we found that the pro-domain（or pro-peptide）of brain-derived neurotrophic factor（BDNF）,which is well-known neurotrophic factor in brain,has a potential ability to facilitate hippocampal long-term depression.Furthermore,a BDNF polymorphism Val66Met,which substitute valine into methionine at 66 amino acid,impacted the biological activity of the BDNF pro-peptide.We lastly discuss the possible roles of BDNF and its pro-peptide in the generation of neural stem cells and progress of ischemia.

The Biological Actions and Mechanisms of Brain-Derived Neurotrophic Factor in Healthy and Disordered Brains

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that elicits neuronal survival and differentiation, synaptic transmission, and the modulation of synaptic plasticity. The biological actions of BDNF are mediated via two distinct receptors: the high-affinity tropomyosin-related kinase B (TrkB) receptor and the low-affinity p75 neurotrophin receptor (p75NTR). Recent findings regarding the actions and mechanisms of BDNF are reviewed here. Activity-dependent synaptic plasticity, as exemplified by long-term potentiation (LTP) and long-term depression (LTD), underlies the cellular mechanism of learning and memory. An accumulating body of evidence shows that BDNF modulates synaptic plasticity. This function requires extracellular neurotrophin release, synaptic activity-dependent local protein synthesis. In addition, a precursor of BDNF, proBDNF, is emerging as a new ligand with biological activities that are distinct from those of BDNF. The proteolytic cleavage of proBDNF is also proposed as a mechanism that determines the direction of BDNF actions. This review discusses the post-translational processing of proBDNF, the modulatory roles of the human BDNF polymorphism Val66Met, recent reports of the novel mechanisms of BDNF expression, and clinical reports showing the roles of BDNF in the blood. Taken together, these data provide new insights into the biological roles of BDNF and its related molecules in the central nervous system.