School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia.
Department of Physiology, Faculty of Medicine, MA`HSA University, Kuala Lumpur, Malaysia.
Curr Pharm Des. 2019;25(26):2808-2827. doi: 10.2174/1381612825666190712181955.
The ubiquitous signaling nucleoside molecule, adenosine is found in different cells of the human body to provide its numerous pharmacological role. The associated actions of endogenous adenosine are largely dependent on conformational change of the widely expressed heterodimeric G-protein-coupled A1, A2A, A2B, and A3 adenosine receptors (ARs). These receptors are well conserved on the surface of specific cells, where potent neuromodulatory properties of this bioactive molecule reflected by its easy passage through the rigid blood-brainbarrier, to simultaneously act on the central nervous system (CNS). The minimal concentration of adenosine in body fluids (30-300 nM) is adequate to exert its neuromodulatory action in the CNS, whereas the modulatory effect of adenosine on ARs is the consequence of several neurodegenerative diseases. Modulatory action concerning the activation of such receptors in the CNS could be facilitated towards neuroprotective action against such CNS disorders. Our aim herein is to discuss briefly pathophysiological roles of adenosine on ARs in the modulation of different CNS disorders, which could be focused towards the identification of potential drug targets in recovering accompanying CNS disorders. Researches with active components with AR modulatory action have been extended and already reached to the bedside of the patients through clinical research in the improvement of CNS disorders. Therefore, this review consist of recent findings in literatures concerning the impact of ARs on diverse CNS disease pathways with the possible relevance to neurodegeneration.
作为一种无处不在的信号核苷分子，腺苷存在于人体的不同细胞中，发挥其众多药理学作用。内源性腺苷的相关作用在很大程度上取决于广泛表达的异二聚体 G 蛋白偶联 A1、A2A、A2B 和 A3 腺苷受体 (AR) 的构象变化。这些受体在特定细胞的表面得到很好的保存，这种生物活性分子在中枢神经系统 (CNS) 中的强大神经调节特性反映在其易于穿过刚性血脑屏障，同时作用于中枢神经系统。体液中腺苷的最小浓度（30-300 nM）足以在中枢神经系统中发挥其神经调节作用，而腺苷对 AR 的调节作用是几种神经退行性疾病的结果。这种受体在中枢神经系统中的激活的调节作用可以促进针对中枢神经系统疾病的神经保护作用。我们在此旨在简要讨论腺苷对 AR 在调节不同中枢神经系统疾病中的病理生理作用，这可能集中在识别伴随中枢神经系统疾病的潜在药物靶点上。具有 AR 调节作用的活性成分的研究已经扩展，并通过临床研究在改善中枢神经系统疾病方面已经达到了患者的床边。因此，本综述包括文献中关于 AR 对多种中枢神经系统疾病途径的影响的最新发现，这些发现可能与神经退行性变有关。
