Almeida-Santos Ana Flavia, Kangussu Lucas M, Campagnole-Santos Maria Jose
Department of Physiology and Biophysics, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Protein Pept Lett. 2017 Nov 17;24(9):841-853. doi: 10.2174/0929866524666170822120258.
A large body of studies characterized the renal and cardiovascular effects of the peptides of the renin-angiotensin system (RAS). We now recognize that, in addition to angiotensin (Ang) II and Ang III, other peptides, such as, Ang-(1-7), Ang-(1-9), Ang IV and Alamandine can mediate actions of the RAS in different tissues, including the brain. Effects elicited by angiotensins in the brain are complex, site specific and dependent on the interaction with selective receptors, angiotensin type 1 receptor (AT1), AT2, Mas or MrgD, which present widespread distribution in the central nervous system. Although the majority of studies indicate a neuroprotective action for the inhibition of angiotensin converting enzyme or blockade of AT1 receptor, recent studies point to the participation of other angiotensin peptides in the pathophysiology of the neurodegenerative diseases.
In this article, we revised the literature to describe recent findings related to the role of RAS in neurodegenerative diseases such as, Parkinson, Alzheimer, Huntington and Multiple Sclerosis.
The results obtained are promising and may stimulate the development of novel and more effective pharmacological tools to prevent and better control neurodegenerative diseases. In this brief review, we present results from studies showing the participation of the RAS with respect to neurodegenerative diseases, such as, Parkinson, Alzheimer, Huntington and Multiple Sclerosis.
Increased RAS activity leading to increase in Ang II levels, may increase the risk of developing PD, AD, HD or MS. However, the alteration in the balance among angiotensin peptides resulting in increasing Ang-(1-7) or Alamandine may represent effective neuroprotective strategy in population groups at high risk or as coadjutant treatment to reduce the progression of these diseases. Although most studies suggest a neuroprotective action for ACE inhibition or AT1 receptor antagonism, many studies will still be needed to characterize the relative importance (and intracellular mechanisms) of each RAS peptide for the pathophysiology of neurodegenerative diseases. The results to date are promising and may lead to new and more effective pharmacological tools to prevent and better control neurodegenerative diseases.
大量研究描述了肾素 - 血管紧张素系统（RAS）肽对肾脏和心血管的影响。我们现在认识到，除了血管紧张素（Ang）II和Ang III外，其他肽，如Ang-(1 - 7)、Ang-(1 - 9)、Ang IV和阿拉曼丁，可在包括大脑在内的不同组织中介导RAS的作用。血管紧张素在大脑中引发的效应复杂、具有位点特异性，且依赖于与选择性受体（血管紧张素1型受体（AT1）、AT2、Mas或MrgD）的相互作用，这些受体在中枢神经系统中广泛分布。尽管大多数研究表明抑制血管紧张素转换酶或阻断AT1受体具有神经保护作用，但最近的研究指出其他血管紧张素肽参与了神经退行性疾病的病理生理学过程。
在本文中，我们查阅了文献，以描述RAS在帕金森病、阿尔茨海默病、亨廷顿病和多发性硬化症等神经退行性疾病中的作用的最新研究结果。
所获得的结果很有前景，可能会促进新型且更有效药物工具的开发，以预防和更好地控制神经退行性疾病。在这篇简短的综述中，我们展示了研究结果，表明RAS参与了帕金森病、阿尔茨海默病、亨廷顿病和多发性硬化症等神经退行性疾病。
RAS活性增加导致Ang II水平升高，可能会增加患帕金森病、阿尔茨海默病、亨廷顿病或多发性硬化症的风险。然而，血管紧张素肽之间平衡的改变导致Ang-(1 - 7)或阿拉曼丁增加，可能是高危人群中有效的神经保护策略，或作为辅助治疗以减缓这些疾病的进展。尽管大多数研究表明抑制血管紧张素转换酶或拮抗AT1受体具有神经保护作用，但仍需要许多研究来确定每种RAS肽在神经退行性疾病病理生理学中的相对重要性（以及细胞内机制）。迄今为止的结果很有前景，可能会带来新的、更有效的药物工具来预防和更好地控制神经退行性疾病。
