Interdisciplinary Laboratory of Medical Investigation (LIIM), Faculty of Medicine, UFMG, Belo Horizonte, MG, Brazil.
Department of Morphology, Laboratory of Neurobiology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Curr Neuropharmacol. 2024;22(1):107-122. doi: 10.2174/1570159X20666220927093815.
Neuropsychiatric disorders, such as mood disorders, schizophrenia, and Alzheimer's disease (AD) and related dementias, are associated to significant morbidity and mortality worldwide. The pathophysiological mechanisms of neuropsychiatric disorders remain to be fully elucidated, which has hampered the development of effective therapies. The Renin Angiotensin System (RAS) is classically viewed as a key regulator of cardiovascular and renal homeostasis. The discovery that RAS components are expressed in the brain pointed out a potential role for this system in central nervous system (CNS) pathologies. The understanding of RAS involvement in the pathogenesis of neuropsychiatric disorders may contribute to identifying novel therapeutic targets.
We aim to report current experimental and clinical evidence on the role of RAS in physiology and pathophysiology of mood disorders, schizophrenia, AD and related dementias. We also aim to discuss bottlenecks and future perspectives that can foster the development of new related therapeutic strategies.
The available evidence supports positive therapeutic effects for neuropsychiatric disorders with the inhibition/antagonism of the ACE/Ang II/AT1 receptor axis or the activation of the ACE2/Ang-(1-7)/Mas receptor axis. Most of this evidence comes from pre-clinical studies and clinical studies lag much behind, hampering a potential translation into clinical practice.
神经精神疾病,如心境障碍、精神分裂症、阿尔茨海默病(AD)和相关痴呆,与全球范围内的高发病率和死亡率相关。神经精神疾病的病理生理机制仍未完全阐明,这阻碍了有效治疗方法的发展。肾素血管紧张素系统(RAS)通常被视为心血管和肾脏稳态的关键调节系统。RAS 成分在大脑中表达的发现,指出了该系统在中枢神经系统(CNS)病理中的潜在作用。对 RAS 参与神经精神疾病发病机制的理解可能有助于确定新的治疗靶点。
我们旨在报告 RAS 在心境障碍、精神分裂症、AD 和相关痴呆的生理和病理生理学中的作用的现有实验和临床证据。我们还旨在讨论可能促进新的相关治疗策略发展的瓶颈和未来展望。
现有证据支持通过抑制/拮抗 ACE/血管紧张素 II/AT1 受体轴或激活 ACE2/血管紧张素-(1-7)/Mas 受体轴对神经精神疾病进行积极的治疗作用。这些证据大多来自于临床前研究,而临床研究滞后很多,这阻碍了其向临床实践的潜在转化。