Fernandez Mercedes, Nigro Manuela, Travagli Alessia, Pasquini Silvia, Vincenzi Fabrizio, Varani Katia, Borea Pier Andrea, Merighi Stefania, Gessi Stefania
Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy.
Department of Chemical, Pharmaceutical and Agricultural Science, University of Ferrara, 44121 Ferrara, Italy.
Pharmaceutics. 2023 Oct 10;15(10):2441. doi: 10.3390/pharmaceutics15102441.
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.
血脑屏障（BBB）是一种生物屏障，通过确保合适的微环境来保护中枢神经系统（CNS）。脑微血管内皮细胞（ECs）控制分子从血液进入脑组织的通道，并调节其浓度-时间曲线，以保证神经元的正常活动、血管生成和神经发生，同时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，因此在中枢神经系统疾病治疗药物的开发中构成了挑战。另一方面，腺苷是一种内源性嘌呤核苷，在大多数身体组织中都有表达，它通过其G蛋白偶联受体（A1、A2A、A2B和A3）发挥作用来调节不同的身体功能。因此，腺苷受体（ARs）被认为是治疗不同代谢、炎症和神经疾病的潜在药物靶点。在中枢神经系统中，A1和A2A由星形胶质细胞、少突胶质细胞、神经元、免疫细胞和内皮细胞表达。此外，腺苷通过其A1和/或A2A受体在局部发挥作用，可能会调节血脑屏障的通透性，当这两种受体同时被激活时，这种作用会增强。这篇综述展示了体内和体外证据，支持AR信号传导作为治疗中枢神经系统疾病时改变内皮屏障通透性的候选机制。
