AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.
AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.
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DOI：
10.18632/aging.101419
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发表时间：
2018-04-17
期刊：
影响因子：
--
通讯作者：
Zhang YD
中科院分区：
文献类型：
--
作者：
Jiang T;Xue LJ;Yang Y;Wang QG;Xue X;Ou Z;Gao Q;Shi JQ;Wu L;Zhang YD
在衰老过程中，由小胶质细胞诱导的慢性神经炎症对大脑是有害的，并且有助于几种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的病因学。ACE 2/Ang-（1-7）/MAS 1轴作为新近发现的一条肾素-血管紧张素系统的轴，在多种病理状态下调节炎症反应中起着重要作用。然而，其与衰老相关的神经炎症的关系目前研究较少。本研究以SAMP 8小鼠作为加速衰老的动物模型，揭示了衰老脑内神经炎症可能与Ang-（1-7）水平降低有关。更重要的是，我们提供的证据表明，AVE 0991，一种非肽类的Ang-（1-7）类似物，通过抑制小胶质细胞介导的炎症反应，通过MAS 1受体依赖的方式，减轻衰老相关的神经炎症。同时，这种保护作用可能归因于AVE 0991诱导的小胶质细胞M2活化。综上所述，这些发现揭示了Ang-（1-7）与老年脑中炎症反应的相关性，并揭示了其非肽类似物AVE 0991在减轻衰老相关神经炎症中的潜力。
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.
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