Research Paper|Volume 10, Issue 4|pp 645—657

AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation

Teng Jiang¹, Liu-Jun Xue^1,², Yang Yang¹, Qing-Guang Wang¹, Xiao Xue¹, Zhou Ou¹, Qing Gao¹, Jian-Quan Shi¹, Liang Wu¹, Ying-Dong Zhang¹

¹Department of Neurology, Nanjing First Hospital Nanjing Medical University, Nanjing, PR China
²Department of Neurology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, PR China

Received: February 9, 2018Accepted: April 14, 2018Published: April 17, 2018

https://doi.org/10.18632/aging.101419

Copyright: © 2018 Jiang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.