The proteins of the mammalian neurotrophin family (nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5)) were originally identified as neuronal survival factors. During the last decade, evidence has accumulated implicating them (especially BDNF) in addition in the regulation of synaptic transmission and synaptogenesis in the CNS. However, a detailed understanding of the secretion of neurotrophins from neurons is required to delineate their role in regulating synaptic function. Some crucial questions that need to be addressed include the sites of neurotrophin secretion (i.e. axonal versus dendritic; synaptic versus extrasynaptic) and the neuronal and synaptic activity patterns that trigger the release of neurotrophins. In this article, we review the current knowledge in the field of neurotrophin secretion, focussing on activity-dependent synaptic release of BDNF. The modality and the site of neurotrophin secretion are dependent on the processing and subsequent targeting of the neurotrophin precursor molecules. Therefore, the available data regarding formation and trafficking of neurotrophins in the secreting neurons are critically reviewed. In addition, we discuss existing evidence that the characteristics of neurotrophin secretion are similar (but not identical) to those of other neuropeptides. Finally, since BDNF has been proposed to play a critical role as an intercellular synaptic messenger in long-term potentiation (LTP) in the hippocampus, we try to reconcile this possible role of BDNF in LTP with the recently described features of synaptic BDNF secretion.

中文翻译：

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神经营养蛋白的分泌：当前事实和未来前景。

哺乳动物神经营养蛋白家族的蛋白质（神经生长因子（NGF），脑源性神经营养因子（BDNF），神经营养蛋白3（NT-3）和神经营养蛋白4/5（NT-4 / 5））最初被鉴定为神经元存活因子。在过去的十年中，除了中枢神经系统中突触传递和突触形成的调控外，已有证据表明它们（尤其是BDNF）。但是，需要详细了解神经元中神经营养蛋白的分泌，以描述其在调节突触功能中的作用。需要解决的一些关键问题包括神经营养蛋白的分泌部位（即轴突与树突；突触与突触外）以及触发神经营养素释放的神经元和突触活动模式。在这篇文章中，我们回顾了神经营养蛋白分泌领域的当前知识，专注于BDNF的活性依赖性突触释放。神经营养蛋白分泌的方式和部位取决于神经营养蛋白前体分子的加工和随后的靶向。因此，严格审查有关分泌神经元中神经营养蛋白的形成和运输的可用数据。此外，我们讨论了现有证据，表明神经营养蛋白分泌的特征与其他神经肽相似（但不相同）。最后，由于已经提出BDNF在海马长时程增强（LTP）中作为细胞间突触信使起关键作用，因此我们试图将BDNF在LTP中的这一可能作用与最近描述的突触BDNF分泌特征相协调。