Neurotrophic factors, a family of secreted proteins that support the growth, survival and differentiation of neurons, have been intensively studied for decades due to the powerful and diverse effects on neuronal physiology, as well as their therapeutic potential. Such efforts have led to a detailed understanding on the molecular mechanisms of neurotrophic factor signaling. One member, brain-derived neurotrophic factor (BDNF) has drawn much attention due to its pleiotropic roles in the central nervous system and implications in various brain disorders. In addition, recent advances linking the rapid-acting antidepressant, ketamine, to BDNF translation and BDNF-dependent signaling, has re-emphasized the importance of understanding the precise details of BDNF biology at the synapse. Although substantial knowledge related to the genetic, epigenetic, cell biological and biochemical aspects of BDNF biology has now been established, certain aspects related to the precise localization and release of BDNF at the synapse have remained obscure. A recent series of genetic and cell biological studies have shed light on the question-the site of BDNF release at the synapse. In this Perspectives article, these new insights will be placed in the context of previously unresolved issues related to BDNF biology, as well as how BDNF may function as a downstream mediator of newer pharmacological agents currently under investigation for treating psychiatric disorders.

中文翻译：

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突触中的BDNF：位置为何重要。

神经营养因子是支持神经元生长，存活和分化的分泌蛋白家族，由于对神经元生理的强大影响及其治疗潜力，人们对其进行了数十年的深入研究。这些努力导致对神经营养因子信号转导的分子机制的详细了解。成员之一，脑源性神经营养因子（BDNF）由于其多效性在中枢神经系统中的作用以及对各种脑部疾病的影响而备受关注。此外，将速效抗抑郁药氯胺酮与BDNF翻译和BDNF依赖性信号传导联系起来的最新进展，再次强调了理解突触中BDNF生物学细节的重要性。尽管有关遗传学，表观遗传学，现已确定BDNF生物学的细胞生物学和生化方面，与BDNF在突触中精确定位和释放有关的某些方面仍然不清楚。最近的一系列遗传和细胞生物学研究阐明了这个问题，即突触中BDNF释放的部位。在这篇“观点”文章中，这些新见解将被放在与BDNF生物学相关的先前未解决问题的背景下，以及BDNF如何作为目前正在研究治疗精神疾病的新型药理学药物的下游介质发挥作用。最近的一系列遗传和细胞生物学研究阐明了这个问题，即突触中BDNF释放的部位。在这篇“观点”文章中，这些新见解将被置于与BDNF生物学相关的先前未解决的问题的背景下，以及BDNF如何作为目前正在研究治疗精神疾病的新型药理学药物的下游介质发挥作用。最近的一系列遗传和细胞生物学研究阐明了这个问题，即突触中BDNF释放的部位。在这篇“观点”文章中，这些新见解将被置于与BDNF生物学相关的先前未解决的问题的背景下，以及BDNF如何作为目前正在研究治疗精神疾病的新型药理学药物的下游介质发挥作用。