Abstract：
Endothelial cells are the building blocks of vessels in the central nervous system (CNS) and form the blood-brain barrier (BBB). An intact BBB limits permeation of large hydrophilic molecules into the CNS. Thus, the healthy BBB is a major obstacle for the treatment of CNS disorders with antibodies, recombinant proteins or viral vectors. Several strategies have been devised to overcome the barrier. A key principle often consists in attaching the therapeutic compound to a ligand of receptors expressed on the BBB, for example, the transferrin receptor (TfR). The fusion molecule will bind to TfR on the luminal side of brain endothelial cells, pass the endothelial layer by transcytosis and be delivered to the brain parenchyma. However, attempts to endow therapeutic compounds with the ability to cross the BBB can be difficult to implement. An alternative and possibly more straight-forward approach is to produce therapeutic proteins in the endothelial cells that form the barrier. These cells are accessible from blood circulation and have a large interface with the brain parenchyma. They may be an ideal production site for therapeutic protein and afford direct supply to the CNS.
摘要：
内皮细胞是中枢神经系统（CNS）中血管的组成部分，并形成血脑屏障（BBB）。完整的BBB限制了大的亲水性分子向CNS的渗透。因此，健康的BBB是用抗体治疗CNS疾病的主要障碍，重组蛋白或病毒载体。已经设计了几种策略来克服该障碍。一个关键原则通常在于将治疗化合物连接到BBB上表达的受体的配体上。例如,转铁蛋白受体(TfR)。融合分子将与脑内皮细胞腔一侧的TfR结合，通过胞吞作用穿过内皮层，并被输送到脑实质。然而,试图赋予治疗性化合物穿越BBB的能力可能难以实现。另一种可能更直接的方法是在形成屏障的内皮细胞中产生治疗性蛋白质。这些细胞可以从血液循环中进入，并且与大脑实质有很大的界面。它们可能是治疗性蛋白质的理想生产场所，并向CNS提供直接供应。
