Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Curr Neuropharmacol. 2009 Dec;7(4):276-85. doi: 10.2174/157015909790031210.
In the central nervous system (CNS), the expression of molecules is strictly regulated during development. Control of the spatiotemporal expression of molecules is a mechanism not only to construct the functional neuronal network but also to adjust the network in response to new information from outside of the individual, i.e., through learning and memory. Among the functional molecules in the CNS, one of the best-studied groups is the neurotrophins, which are nerve growth factor (NGF)-related gene family molecules. Neurotrophins include NGF, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and NT-4/5 in the mammal. Among neurotrophins and their receptors, BDNF and tropomyosin-related kinases B (TrkB) are enriched in the CNS. In the CNS, the BDNF-TrkB signaling pathway fulfills a wide variety of functions throughout life, such as cell survival, migration, outgrowth of axons and dendrites, synaptogenesis, synaptic transmission, and remodeling of synapses. Although the same ligand and receptor, BDNF and TrkB, act in these various developmental events, we do not yet understand what kind of mechanism provokes the functional multiplicity of the BDNF-TrkB signaling pathway. In this review, we discuss the mechanism that elicits the variety of functions performed by the BDNF-TrkB signaling pathway in the CNS as a tool of pharmacological therapy.
在中枢神经系统（CNS）中，分子的表达在发育过程中受到严格调控。分子时空表达的控制不仅是构建功能性神经网络的机制，也是响应个体外部新信息（即通过学习和记忆）调节网络的机制。在 CNS 中的功能分子中，研究最多的一组是神经营养因子，它们是神经生长因子（NGF）相关基因家族的分子。神经营养因子包括哺乳动物中的 NGF、脑源性神经营养因子（BDNF）、神经营养因子 3（NT-3）和 NT-4/5。在神经营养因子及其受体中，BDNF 和原肌球蛋白相关激酶 B（TrkB）在 CNS 中丰富存在。在 CNS 中，BDNF-TrkB 信号通路在整个生命周期中发挥着多种多样的功能，例如细胞存活、迁移、轴突和树突的生长、突触形成、突触传递以及突触重塑。尽管相同的配体和受体（BDNF 和 TrkB）在这些不同的发育事件中起作用，但我们尚不清楚什么样的机制引发了 BDNF-TrkB 信号通路的功能多样性。在这篇综述中，我们讨论了引发 BDNF-TrkB 信号通路在 CNS 中发挥各种功能的机制，将其作为药理学治疗的工具。
