Author(s)

Toshiyuki Mizui^1,2, Yuichiro Tanima^1,2, Hiroko Komatsu³, Haruko Kumanogoh^1,2*, Masami Kojima^1,2

¹Bio-Interface Research Group, Health Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ikeda, Japan.
²Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Kawaguchi, Japan.
³Global Discovery Research, Neuroscience and General Medicine Product Creation Unit, Eisai Product Creation Systems, Eisai Co., Ltd., Tsukuba, Japan.

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.

Component, Brain-Derived Neurotrophic Factor (BDNF), Tropomyosin-Related Kinase B (TrkB), Synaptic Plasticity, Polymorphism, Proteolytic Cleavage

Mizui, T. , Tanima, Y. , Komatsu, H. , Kumanogoh, H. and Kojima, M. (2014) The Biological Actions and Mechanisms of Brain-Derived Neurotrophic Factor in Healthy and Disordered Brains. Neuroscience and Medicine, 5, 183-195. doi: 10.4236/nm.2014.54021.