Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
Department of Psychiatry, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
J Neurochem. 2023 Jul;166(2):138-155. doi: 10.1111/jnc.15806. Epub 2023 Mar 27.
The renin-angiotensin system (RAS) plays essential roles in maintaining peripheral cardiovascular homeostasis, with its potential roles in the brain only being recognized more recently. Angiotensin-I-converting enzyme (ACE) is the main component of the RAS, and it has been implicated in various disorders of the brain. ACE and other RAS components, including the related enzyme ACE2, angiotensin peptides and their respective receptors, can participate in the pathological state, as well as with potential to contribute to neuroprotection and/or to complement existing treatments for psychiatric illness. In this narrative review, we aimed to identify the main studies describing the functions of the RAS and ACEs in the brain and their association with brain disorders. These include neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. We also discuss the possible association of a functional polymorphism of the ACE gene with these brain diseases and the relevance of the neuroprotective and anti-inflammatory properties of ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs). Based on this, we conclude that there is significant potential value to the inclusion of ACEis and/or ARBs as a novel integrated approach for the treatment of various disorders of the brain, and particularly for psychiatric illness.
肾素-血管紧张素系统（RAS）在维持外周心血管稳态方面发挥着重要作用，其在大脑中的潜在作用最近才被认识到。血管紧张素转换酶（ACE）是 RAS 的主要组成部分，它与大脑的各种疾病有关。ACE 和其他 RAS 成分，包括相关酶 ACE2、血管紧张素肽及其各自的受体，都可以参与病理状态，并有可能有助于神经保护和/或补充现有的精神疾病治疗方法。在这篇叙述性综述中，我们旨在确定描述 RAS 和 ACE 在大脑中的功能及其与大脑疾病关联的主要研究。这些疾病包括神经退行性疾病，如帕金森病和阿尔茨海默病，以及精神疾病，如精神分裂症、双相情感障碍和抑郁症。我们还讨论了 ACE 基因的一种功能性多态性与这些脑部疾病的可能关联，以及 ACE 抑制剂（ACEIs）和血管紧张素受体阻滞剂（ARBs）的神经保护和抗炎特性的相关性。基于这些，我们得出结论，将 ACEIs 和/或 ARBs 作为一种治疗各种脑部疾病的新的综合方法，特别是治疗精神疾病，具有重要的潜在价值。
