Brain Renin-Angiotensin System at the Intersect of Physical and Cognitive Frailty.
Brain Renin-Angiotensin System at the Intersect of Physical and Cognitive Frailty.
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脑和认知脆弱的相交的脑肾素 - 血管紧张素系统。
DOI：
10.3389/fnins.2020.586314
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发表时间：
2020
影响因子：
4.3
通讯作者：
Abadir PM
中科院分区：
文献类型：
--
作者：
Cosarderelioglu C;Nidadavolu LS;George CJ;Oh ES;Bennett DA;Walston JD;Abadir PM
肾素-血管紧张素系统（RAS）最初被认为是调节水和电解质平衡、全身血管阻力、血压和心血管稳态的内分泌系统的一部分。后来发现，除了内分泌RAS外，大脑中还存在内分泌型和局部型RAS。这种大脑特异性 RAS 主要通过四种血管紧张素受体亚型发挥作用，在大脑稳态中发挥重要作用。 AT1R、AT2R、MasR 和 AT4R。这些受体具有相反的作用； AT1R 促进血管收缩、增殖、炎症和氧化应激，而 AT2R 和 MasR 抵消 AT1R 的影响。 AT4R 对于多巴胺和乙酰胆碱的释放至关重要，并介导学习和记忆巩固。因此，与衰老相关的血管紧张素受体亚型失调可能会导致不良的临床结果，例如阿尔茨海默病和由于过度氧化应激、神经炎症、内皮功能障碍、小胶质细胞极化和神经递质分泌改变而导致的虚弱。在这篇文章中，我们从这个角度回顾了大脑 RAS。在讨论了各个大脑 RAS 成分的功能及其在细胞内和颅内的位置之后，我们重点关注大脑 RAS 通过氧化应激、神经炎症和血管功能障碍与衰老、虚弱和特定神经退行性疾病（如阿尔茨海默病、帕金森病和血管性认知障碍）之间的关系。最后，我们讨论了 RAS 调节药物对大脑 RAS 的影响及其在新型治疗方法中的应用。
The renin–angiotensin system (RAS) was initially considered to be part of the endocrine system regulating water and electrolyte balance, systemic vascular resistance, blood pressure, and cardiovascular homeostasis. It was later discovered that intracrine and local forms of RAS exist in the brain apart from the endocrine RAS. This brain-specific RAS plays essential roles in brain homeostasis by acting mainly through four angiotensin receptor subtypes; AT1R, AT2R, MasR, and AT4R. These receptors have opposing effects; AT1R promotes vasoconstriction, proliferation, inflammation, and oxidative stress while AT2R and MasR counteract the effects of AT1R. AT4R is critical for dopamine and acetylcholine release and mediates learning and memory consolidation. Consequently, aging-associated dysregulation of the angiotensin receptor subtypes may lead to adverse clinical outcomes such as Alzheimer’s disease and frailty via excessive oxidative stress, neuroinflammation, endothelial dysfunction, microglial polarization, and alterations in neurotransmitter secretion. In this article, we review the brain RAS from this standpoint. After discussing the functions of individual brain RAS components and their intracellular and intracranial locations, we focus on the relationships among brain RAS, aging, frailty, and specific neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and vascular cognitive impairment, through oxidative stress, neuroinflammation, and vascular dysfunction. Finally, we discuss the effects of RAS-modulating drugs on the brain RAS and their use in novel treatment approaches.
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影响因子：
11.2
作者：
Arvanitakis Z;Wang HY;Capuano AW;Khan A;Taïb B;Anokye-Danso F;Schneider JA;Bennett DA;Ahima RS;Arnold SE
通讯作者：
Arnold SE
影响因子：
11.2
作者：
ALLEN, AM;MACGREGOR, DP;MENDELSOHN, FAO
通讯作者：
MENDELSOHN, FAO
DOI：
10.1124/jpet.112.197483
发表时间：
2013-02-01
影响因子：
3.5
作者：
Alhusban, Ahmed;Kozak, Anna;Fagan, Susan C.
通讯作者：
Fagan, Susan C.
影响因子：
3.3
作者：
Akimoto, M;Baba, A;Matsuki, N
通讯作者：
Matsuki, N
影响因子：
2.9
作者：
Abrahao, Mariana Vieira;Teixeira dos Santos, Natalia Fernanda;Afeche, Solange Castro
通讯作者：
Afeche, Solange Castro