Since its discovery, brain-derived neurotrophic factor (BDNF) has spawned a literature that now spans 35 years of research. While all neurotrophins share considerable overlap in sequence homology and their processing, BDNF has become the most widely studied neurotrophin because of its broad roles in brain homeostasis, health, and disease. Although research on BDNF has produced thousands of articles, there remain numerous long-standing questions on aspects of BDNF molecular biology and signaling. Here we provide a comprehensive review, including both a historical narrative and a forward-looking perspective on advances in the actions of BDNF within the brain. We specifically review BDNF's gene structure, peptide composition (including domains, posttranslational modifications and putative motif sites), mechanisms of transport, signaling pathway recruitment, and other recent developments including the functional effects of genetic variation and the discovery of a new BDNF prodomain ligand. This body of knowledge illustrates a highly conserved and complex role for BDNF within the brain, that promotes the idea that the neurotrophin biology of BDNF is diverse and that any disease involvement is likely to be equally multifarious.

中文翻译：

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脑源性神经营养因子（BDNF）：对调节和遗传变异的新颖见解。

自发现以来，脑源性神经营养因子（BDNF）催生了至今已有35年研究历史的文献。尽管所有神经营养蛋白在序列同源性和它们的加工过程中都有相当大的重叠，但由于BDNF在脑稳态，健康和疾病中的广泛作用，它已成为研究最广泛的神经营养蛋白。尽管关于BDNF的研究已经发表了数千篇文章，但是关于BDNF分子生物学和信号传导方面仍然存在许多长期存在的问题。在这里，我们提供了全面的综述，包括关于BDNF在大脑中的作用进展的历史叙述和前瞻性观点。我们专门审查了BDNF的基因结构，肽组成（包括结构域，翻译后修饰和推定的基序位点），转运机制，信号通路募集以及其他近期发展，包括遗传变异的功能效应和新的BDNF前域配体的发现。这种知识体系说明了BDNF在大脑中的高度保守和复杂的作用，这提倡了BDNF的神经营养素生物学是多种多样的，并且任何疾病的侵袭都可能同样多种多样。