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肾素-血管紧张素系统调节剂在阿尔茨海默病性痴呆中的治疗意义

Therapeutic Implications of Renin-Angiotensin System Modulators in Alzheimer's Dementia.

作者信息

Ababei Daniela-Carmen, Bild Veronica, Macadan Ioana, Vasincu Alexandru, Rusu Răzvan-Nicolae, Blaj Mihaela, Stanciu Gabriela Dumitrița, Lefter Radu-Marian, Bild Walther

机构信息

Department of Pharmacodynamics and Clinical Pharmacy, "Grigore T. Popa" University of Medicine and Pharmacy, 16 Universitatii Street, 700115 Iasi, Romania.

Center of Biomedical Research, Romanian Academy, Iasi Branch, 8 Carol I Avenue, 700506 Iasi, Romania.

出版信息

Pharmaceutics. 2023 Sep 6;15(9):2290. doi: 10.3390/pharmaceutics15092290.

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)因其在神经退行性疾病(包括阿尔茨海默病(AD))中的潜在作用,在传统心血管作用之外引起了广泛关注。本综述探讨了RAS调节剂的治疗意义,特别关注血管紧张素转换酶抑制剂(ACEIs)、血管紧张素受体阻滞剂(ARBs)和肾素抑制剂在AD中的作用。常用于治疗高血压的ACEIs通过降低血管紧张素(Ang)II水平在AD治疗中显示出前景。这种降低具有重要意义,因为Ang II会导致神经炎症、氧化应激和β-淀粉样蛋白(Aβ)积累,这些都与AD发病机制有关。以血管舒张作用闻名的ARBs通过阻断Ang II受体发挥神经保护作用,改善AD模型中的脑血流量和认知功能下降。肾素抑制剂通过靶向RAS的起始步骤提供了一种新方法,显示出抗炎和抗氧化作用,减轻AD的退行性变。临床前研究表明,RAS调节对神经炎症、神经元损伤、认知功能和Aβ代谢具有积极影响。关于RAS调节剂在AD中的临床试验有限,但结果令人鼓舞,ARBs在减少认知功能下降方面比ACEIs更有效。ACEIs、ARBs和肾素抑制剂在RAS调节中的不同作用为AD治疗干预提供了一条有前景的途径,需要进一步研究以潜在地改变AD治疗策略。

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