AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates agin-grelated neuroinflammation
AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates agin-grelated neuroinflammation
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AVE0991 是 Ang-(1-7) 的非肽类似物，可减轻年龄相关的神经炎症
DOI：
10.18632/aging/101419
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发表时间：
2018
期刊：
影响因子：
5.2
通讯作者：
Zhang Ying-Dong
中科院分区：
文献类型：
--
作者：
Jiang Teng;Xue Liu-Jun;Yang Yang;Wang Qing-Guang;Xue Xiao;Ou Zhou;Gao Qing;Shi Jian-Quan;Wu Liang;Zhang Ying-Dong
在衰老过程中，小胶质细胞诱导的慢性神经炎症对大脑有害，并导致一些与衰老相关的神经退行性疾病，如阿尔茨海默病和帕金森病。作为新发现的肾素-血管紧张素系统轴，ACE2/Ang-(1-7)/MAS1轴在调节各种病理条件下的炎症反应中起着至关重要的作用。然而，到目前为止，它与衰老相关的神经炎症的关系研究较少。本研究利用SAMP8小鼠这一加速衰老的动物模型，揭示了老年脑内神经炎症可能与Ang-(1-7)水平降低有关。更重要的是，我们提供了AVE0991的证据，AVE0991是Ang-(1-7)的非肽类似物，通过MAS1受体依赖的方式抑制小胶质细胞介导的炎症反应，从而减轻衰老相关的神经炎症。这种保护作用可能与AVE0991诱导的小胶质细胞M2活化有关。综上所述，这些发现揭示了Ang-(1-7)与老年人脑部炎症反应的关系，并揭示了其非肽类似物AVE0991在减轻与衰老相关的神经炎症方面的潜力。
During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.