Abstract：
The field of peptides exploded in the 1970\'s and has continued to be a major area of discovery. Among the early discoveries was that peptides administered peripherally could affect brain functions. This led Kastin to propose that peptides could cross the blood-brain barrier (BBB). Although initially very controversial, Kastin, I, and others demonstrated not only that peptides can cross the BBB, but elucidated many fundamental characteristics of that passage. That work was in large part the basis of the 2022 Viktor Mutt Lectureship. Here, we review some of the early work with current updates on topics related to the penetration of peptides across the BBB. We briefly review mechanisms by which peripherally administered peptides can affect brain function without crossing the BBB, and then review the major mechanisms by which peptides and their analogs have been show to cross the BBB: transmembrane diffusion, saturable transport, and adsorptive transcytosis. Saturable transport systems are adaptable to physiologic changes and can be altered by disease states. In particular, the transport across the BBB of insulin and of pituitary adenylate cyclase activating polypeptide (PACAP) illustrate many of the concepts regarding peptide transport across the BBB.
摘要：
肽领域在1970年代爆发，并一直是一个主要的发现领域。早期发现之一是外周施用的肽可以影响脑功能。这导致Kastin提出肽可以穿过血脑屏障（BBB）。虽然最初非常有争议，Kastin,I,其他人不仅证明了肽可以穿过BBB，但阐明了这篇文章的许多基本特征。这项工作在很大程度上是2022年ViktorMutt演讲的基础。这里,我们回顾了一些早期的工作，以及与肽在BBB中渗透相关的主题的最新更新。我们简要回顾了外周施用的肽可以影响脑功能而不穿过BBB的机制。然后回顾肽和它们的类似物已经显示出穿过BBB的主要机制：跨膜扩散，可饱和的运输，和吸附性胞吞作用。可饱和运输系统可适应生理变化，并且可以因疾病状态而改变。特别是,胰岛素和垂体腺苷酸环化酶激活多肽(PACAP)跨BBB转运说明了许多关于肽跨BBB转运的概念.
