title: Neurobiological actions by three distinct subtypes of brain-derived neurotrophic factor: Multi-ligand model of growth factor signaling.
abstract: Brain-derived neurotrophic factor (BDNF) is one of the most active members of the neurotrophin family. BDNF not only regulates neuronal survival and differentiation, but also functions in activity-dependent plasticity processes such as long-term potentiation (LTP), long-term depression (LTD), learning, and memory. Like other growth factors, BDNF is produced by molecular and cellular mechanisms including transcription and translation, and functions as a bioactive molecule in the nervous system. Among these mechanisms, a particular post-translational mechanism, namely the conversion of precursor BDNF into mature BDNF by proteolytic cleavage, was not fully understood. In this review, we discuss the manner through which this post-translational mechanism alters the biological actions of BDNF protein. In addition to the initially elucidated findings on BDNF, the biological roles of precursor BDNF and the BDNF pro-peptide, especially synaptic plasticity, will be extensively discussed. Recent findings on the BDNF pro-peptide will provide new insights for understanding the mechanisms of action of the pro-peptides of growth factors.
authors.affiliation: Biomedical Research Institute, Advanced Industrial Science and Technology (AIST), Osaka 563-8577, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan. Electronic address: t-mizui@aist.go.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Mizui
authors.affiliation: Department of Systems Life Engineering, Maebashi Institute of Technology, Gunma 371-0816, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Biomedical Research Institute, Advanced Industrial Science and Technology (AIST), Osaka 563-8577, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Kumanogoh
authors.affiliation: Biomedical Research Institute, Advanced Industrial Science and Technology (AIST), Osaka 563-8577, Japan; Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi 332-0012, Japan. Electronic address: m-kojima@aist.go.jp.
authors.forename: Masami
authors.initials: M
authors.lastname: Kojima
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D036881:Long-Term Synaptic Depression; D009473:Neuronal Plasticity; D011110:Polymorphism, Genetic; D011498:Protein Precursors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D011498:Protein Precursors; C426674:brain-derived neurotrophic factor precursor
keywords: BDNF; Hippocampus; Long-term depression; Polymorphism; Pro-peptide