PDF(Pubmed)
Abstract：
The Renin-Angiotensin System (RAS) has attracted considerable interest beyond its traditional cardiovascular role due to emerging data indicating its potential involvement in neurodegenerative diseases, including Alzheimer\'s dementia (AD). This review investigates the therapeutic implications of RAS modulators, specifically focusing on angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and renin inhibitors in AD. ACEIs, commonly used for hypertension, show promise in AD by reducing angiotensin (Ang) II levels. This reduction is significant as Ang II contributes to neuroinflammation, oxidative stress, and β-amyloid (Aβ) accumulation, all implicated in AD pathogenesis. ARBs, known for vasodilation, exhibit neuroprotection by blocking Ang II receptors, improving cerebral blood flow and cognitive decline in AD models. Renin inhibitors offer a novel approach by targeting the initial RAS step, displaying anti-inflammatory and antioxidant effects that mitigate AD degeneration. Preclinical studies demonstrate RAS regulation\'s favorable impact on neuroinflammation, neuronal damage, cognitive function, and Aβ metabolism. Clinical trials on RAS modulators in AD are limited, but with promising results, ARBs being more effective that ACEIs in reducing cognitive decline. The varied roles of ACEIs, ARBs, and renin inhibitors in RAS modulation present a promising avenue for AD therapeutic intervention, requiring further research to potentially transform AD treatment strategies.
摘要：
肾素-血管紧张素系统（RAS）除了其传统的心血管作用外，还吸引了相当大的兴趣，因为新兴的数据表明其可能参与神经退行性疾病。包括老年痴呆症（AD）。这篇综述研究了RAS调节剂的治疗意义，特别关注血管紧张素转换酶抑制剂（ACEI），血管紧张素受体阻滞剂（ARB），和肾素抑制剂在AD中的作用。ACEIs,常用于高血压，通过降低血管紧张素（Ang）II水平在AD中显示希望。这种减少是显著的，因为AngII有助于神经炎症，氧化应激，和β-淀粉样蛋白（Aβ）的积累，都与AD发病机制有关。ARBs,以血管舒张而闻名，通过阻断AngII受体表现出神经保护作用，改善AD模型的脑血流量和认知功能下降。肾素抑制剂通过靶向初始RAS步骤提供了一种新的方法，显示减轻AD变性的抗炎和抗氧化作用。临床前研究表明RAS调节对神经炎症的有利影响，神经元损伤，认知功能,和Aβ代谢。AD中RAS调节剂的临床试验有限，但是有了有希望的结果，ARB在减少认知能力下降方面比ACEI更有效。ACEI的不同角色，ARBs,RAS调节中的肾素抑制剂为AD治疗干预提供了有希望的途径，需要进一步研究以可能改变AD治疗策略。
