Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA.
Department of Neurology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Int J Mol Sci. 2018 Mar 15;19(3):876. doi: 10.3390/ijms19030876.
For many years, modulators of the renin angiotensin system (RAS) have been trusted by clinicians for the control of essential hypertension. It was recently demonstrated that these modulators have other pleiotropic properties independent of their hypotensive effects, such as enhancement of cognition. Within the brain, different components of the RAS have been extensively studied in the context of neuroprotection and cognition. Interestingly, a crosstalk between the RAS and other systems such as cholinergic, dopaminergic and adrenergic systems have been demonstrated. In this review, the preclinical and clinical evidence for the impact of RAS modulators on cognitive impairment of multiple etiologies will be discussed. In addition, the expression and function of different receptor subtypes within the RAS such as: Angiotensin II type I receptor (AT1R), Angiotensin II type II receptor (AT2R), Angiotensin IV receptor (AT4R), Mas receptor (MasR), and Mas-related-G protein-coupled receptor (MrgD), on different cell types within the brain will be presented. We aim to direct the attention of the scientific community to the plethora of evidence on the importance of the RAS on cognition and to the different disease conditions in which these agents can be beneficial.
多年来，肾素-血管紧张素系统 (RAS) 的调节剂一直受到临床医生的信赖，用于控制原发性高血压。最近有研究表明，这些调节剂具有独立于其降压作用的其他多效性特性，例如增强认知能力。在大脑中，RAS 的不同成分在神经保护和认知方面已经得到了广泛研究。有趣的是，已经证明 RAS 和其他系统（如胆碱能、多巴胺能和肾上腺素能系统）之间存在串扰。在这篇综述中，将讨论 RAS 调节剂对多种病因引起的认知障碍的影响的临床前和临床证据。此外，还将介绍 RAS 中的不同受体亚型（如血管紧张素 II 型 1 型受体 (AT1R)、血管紧张素 II 型 2 型受体 (AT2R)、血管紧张素 IV 受体 (AT4R)、Mas 受体 (MasR) 和 Mas 相关 G 蛋白偶联受体 (MrgD)）在大脑内不同细胞类型上的表达和功能。我们旨在引起科学界对 RAS 对认知的重要性以及这些药物在不同疾病状况下的有益性的大量证据的关注。
