Banks William A
Geriatric Research Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle 98108, WA, USA; Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98104, USA.
Peptides. 2023 Nov;169:171079. doi: 10.1016/j.peptides.2023.171079. Epub 2023 Aug 19.
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.
肽领域在20世纪70年代蓬勃发展，并一直是一个重要的发现领域。早期的发现之一是，外周给予的肽可以影响脑功能。这使得卡斯汀提出肽可以穿过血脑屏障（BBB）。尽管最初极具争议，但卡斯汀、我以及其他人不仅证明了肽可以穿过血脑屏障，还阐明了该过程的许多基本特征。这项工作很大程度上是2022年维克托·穆特讲座的基础。在此，我们回顾一些早期工作，并对与肽穿过血脑屏障相关主题的最新进展进行介绍。我们简要回顾外周给予的肽在不穿过血脑屏障的情况下影响脑功能的机制，然后回顾肽及其类似物已被证明穿过血脑屏障的主要机制：跨膜扩散、可饱和转运和吸附转胞吞作用。可饱和转运系统能适应生理变化，并可因疾病状态而改变。特别是，胰岛素和垂体腺苷酸环化酶激活多肽（PACAP）穿过血脑屏障的过程阐释了许多关于肽穿过血脑屏障的概念。
