PDF(Pubmed)
Abstract：
The blood-brain barrier (BBB) is a biological barrier that protects the central nervous system (CNS) by ensuring an appropriate microenvironment. Brain microvascular endothelial cells (ECs) control the passage of molecules from blood to brain tissue and regulate their concentration-versus-time profiles to guarantee proper neuronal activity, angiogenesis and neurogenesis, as well as to prevent the entry of immune cells into the brain. However, the BBB also restricts the penetration of drugs, thus presenting a challenge in the development of therapeutics for CNS diseases. On the other hand, adenosine, an endogenous purine-based nucleoside that is expressed in most body tissues, regulates different body functions by acting through its G-protein-coupled receptors (A1, A2A, A2B and A3). Adenosine receptors (ARs) are thus considered potential drug targets for treating different metabolic, inflammatory and neurological diseases. In the CNS, A1 and A2A are expressed by astrocytes, oligodendrocytes, neurons, immune cells and ECs. Moreover, adenosine, by acting locally through its receptors A1 and/or A2A, may modulate BBB permeability, and this effect is potentiated when both receptors are simultaneously activated. This review showcases in vivo and in vitro evidence supporting AR signaling as a candidate for modifying endothelial barrier permeability in the treatment of CNS disorders.
摘要：
血脑屏障（BBB）是通过确保适当的微环境来保护中枢神经系统（CNS）的生物屏障。脑微血管内皮细胞（EC）控制分子从血液到脑组织的通道，并调节其浓度-时间曲线，以确保适当的神经元活动，血管生成和神经发生，以及防止免疫细胞进入大脑。然而,血脑屏障也限制了药物的渗透，因此对CNS疾病的治疗方法的发展提出了挑战。另一方面,腺苷,在大多数身体组织中表达的内源性嘌呤核苷，通过其G蛋白偶联受体（A1，A2A，A2B和A3）。因此，腺苷受体（ARs）被认为是治疗不同代谢的潜在药物靶标。炎症和神经系统疾病。在中枢神经系统，A1和A2A由星形胶质细胞表达，少突胶质细胞,神经元，免疫细胞和ECs。此外，腺苷,通过其受体A1和/或A2A局部作用，可以调节BBB通透性，当两个受体同时激活时，这种作用就会增强。这篇综述展示了体内和体外证据，支持AR信号传导作为治疗CNS疾病中改变内皮屏障通透性的候选者。
