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.