Background: The Renin-Angiotensin System (RAS) comprises a complex molecular cascade with two counter-regulatory axes, the classical and the alternative. Angiotensin II and Angiotensin-(1-7), the main peptides of the RAS, exert opposite effects in multiple organs and systems, including the cardiovascular, renal, pulmonary, and immune systems. Strong evidence supports the hypothesis of a local RAS in the Central Nervous System (CNS) and its modulatory roles in neuroendocrinology and neurotransmission.

Objective: In this narrative review, we provide a comprehensive approach to experimental and clinical data regarding RAS molecule expression and their possible roles in the physiology and physiopathology of CNS diseases.

Methods: This non-systematic review summarizes evidence on RAS implications in CNS diseases and their possible relationships with COVID-19.

Results: We divided the possible RAS mechanisms in distinct conditions during the lifespan, approaching from congenital infections to neurodegenerative alterations, passing through mood disorders and cerebrovascular diseases. We also gathered current evidence about the possible effects of RAS in Covid-19, particularly in cases with neurological manifestations.

Conclusion: Although there are limitations and controversies, the analysis of RAS mechanisms in the CNS certainly represents an interesting field of research. However, further investigation is necessary to support the noteworthy interactions and provide a better comprehension of the cross-talk between RAS and the CNS. Investigations in this research field may shed light on the novel therapeutic targets.

背景：肾素-血管紧张素系统 (RAS) 包含一个复杂的分子级联，具有两个反调节轴，经典轴和替代轴。血管紧张素 II 和血管紧张素-(1-7) 是 RAS 的主要肽，在包括心血管、肾脏、肺和免疫系统在内的多个器官和系统中发挥相反的作用。强有力的证据支持中枢神经系统 (CNS) 中的局部 RAS 及其在神经内分泌学和神经传递中的调节作用的假设。

目的：在这篇叙述性综述中，我们提供了一种综合方法来处理关于 RAS 分子表达及其在 CNS 疾病生理学和病理生理学中可能的作用的实验和临床数据。

方法：这项非系统性综述总结了 RAS 对 CNS 疾病的影响及其与 COVID-19 可能关系的证据。

结果：我们在生命周期的不同条件下划分了可能的 RAS 机制，从先天性感染到神经退行性改变，通过情绪障碍和脑血管疾病。我们还收集了有关 RAS 在 Covid-19 中可能产生的影响的最新证据，尤其是在有神经系统表现的病例中。

结论：尽管存在局限性和争议，但对 CNS 中 RAS 机制的分析无疑代表了一个有趣的研究领域。然而，需要进一步调查以支持值得注意的相互作用并更好地理解 RAS 和 CNS 之间的串扰。该研究领域的调查可能会揭示新的治疗靶点。