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

Jiang, Teng; Xue, Liujun; Yang, Yang; Wang, Qingguang; Xue, Xiao; Ou, Zhou; Gao, Qing; Shi, Jian-Quan; Wu, Liang

doi:10.18632/aging.101419

Cited by 38 publications

(25 citation statements)

References 43 publications

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“…The top three ranked multidimensional proteins that could represent effective age-related disease interdiction targets were, arginine vasopressin receptor 1B (AVPR1B), MAS1 proto-oncogene, GPCR (MAS1) and RLN3, the cognate ligand for the RXFP3 (Figure 11C). It is interesting to note that the MAS1 [196] and arginine vasopressin receptors [197] have recently been implicated in age-related disorder amelioration. In this context, using an unbiased multidimensional approach it is tantalizing to anticipate that therapeutic modulation of the RXFP3 may also hold significant promise for the attenuation of multiple age-related diseases.…”

Section: Discussionmentioning

confidence: 99%

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Gastel

Leysen

Santos‐Otte

et al. 2019

Aging

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DNA damage response (DDR) processes, often caused by oxidative stress, are important in aging and -related disorders. We recently showed that G protein-coupled receptor (GPCR) kinase interacting protein 2 (GIT2) plays a key role in both DNA damage and oxidative stress. Multiple tissue analyses in GIT2KO mice demonstrated that GIT2 expression affects the GPCR relaxin family peptide 3 receptor (RXFP3), and is thus a therapeutically-targetable system. RXFP3 and GIT2 play similar roles in metabolic aging processes. Gaining a detailed understanding of the RXFP3-GIT2 functional relationship could aid the development of novel anti-aging therapies. We determined the connection between RXFP3 and GIT2 by investigating the role of RXFP3 in oxidative stress and DDR. Analyzing the effects of oxidizing (H2O2) and DNA-damaging (camptothecin) stressors on the interacting partners of RXFP3 using Affinity Purification-Mass Spectrometry, we found multiple proteins linked to DDR and cell cycle control. RXFP3 expression increased in response to DNA damage, overexpression, and Relaxin 3-mediated stimulation of RXFP3 reduced phosphorylation of DNA damage marker H2AX, and repair protein BRCA1, moderating DNA damage. Our data suggests an RXFP3-GIT2 system that could regulate cellular degradation after DNA damage, and could be a novel mechanism for mitigating the rate of age-related damage accumulation.

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Section: Discussionmentioning

confidence: 99%

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Gastel

Leysen

Santos‐Otte

et al. 2019

Aging

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“…Hence, it was of great signi cance to study the role of Mas receptor in acute allergic airway in ammation. Considering that Ang-(1-7) exerted a short duration of biological effect in vivo for rapid degradation by ACE which was rich in lung [34], we employed AVE0991, a synthetic non-peptide agonist of Mas receptor, in subsequent experiments to further evaluate the role of Mas receptor in acute allergic airway in ammation. Different from studies in MG Rodrigue-Machado [17,18], we further performed the immuno uorescence double staining to co-localize Mas receptor with EpCAM, which con rmed that Mas receptor mainly acted on airway epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Mas Receptor Activation Attenuates Allergic Airway Inflammation via Inhibiting JNK/CCL2-induced Macrophage Recruitment

Hong

Chen

Shi

et al. 2020

Preprint

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Background: Defective absorption of acute allergic airway inflammation is involved in the initiation and development of chronic asthma. After allergen exposure, there is a rapid recruitment of macrophages around the airways, which promote acute inflammatory responses. The Ang-(1-7)/Mas receptor axis reportedly plays protective roles in various tissue inflammation and remodeling processes in vivo. However, the exact role of Mas receptor and their underlying mechanisms during the pathology of acute allergic airway inflammation remains unclear. Methods: Mas receptor expression was assessed in ovalbumin-induced acute asthmatic murine model. Then we estimated the anti-inflammatory role of Mas receptor in vivo and explored expressions of several known inflammatory cytokines as well as phosphorylation levels of MAPK pathways. Mas receptor functions and underlying mechanisms were studied further in the human bronchial epithelial cell line (16HBE).Results: Mas receptor expression decreased in acute allergic airway inflammation. Multiplex immunofluorescence co-localized Mas receptor and EpCAM, indicated that Mas receptor may function in the bronchial epithelium. Activating Mas receptor through AVE0991 significantly alleviated macrophage infiltration in airway inflammation, accompanied with down-regulation of CCL2 and phosphorylation levels of MAPK pathways. Further studies in 16HBE showed that AVE0991 pre-treatment inhibited LPS-induced or anisomycin-induced CCL2 increase and THP-1 macrophages migration via JNK pathways.Conclusion: Our findings suggested that Mas receptor activation significantly attenuated CCL2 dependent macrophage recruitments in acute allergic airway inflammation through JNK pathways, which indicated that Mas receptor, CCL2 and phospho-JNK could be potential targets against allergic airway inflammation.

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“…In a recent study, AVE0991 was found to attenuate the neuroinflammation related to the ageing process through the suppression of the microglial-mediated inflammatory response [127]. In addition to this, the intranasal administration of ACE0991 in the animal study reduced oxidative stress and neural apoptosis, and improved neurobehavioral scores in brain injury after subarachnoid hemorrhage.…”

Section: New Perspectives In Targeting Ras Mas Atr2 and Atr4 Recmentioning

confidence: 99%

Role of the Angiotensin Pathway and its Target Therapy in Epilepsy Management

Krasniqi

Daci

2019

IJMS

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Despite extensive research on epileptogenesis, there is still a need to investigate new pathways and targeted therapeutic approaches in this complex process. Inflammation, oxidative stress, neurotoxicity, neural cell death, gliosis, and blood–brain barrier (BBB) dysfunction are the most common causes of epileptogenesis. Moreover, the renin–angiotensin system (RAS) affects the brain’s physiological and pathological conditions, including epilepsy and its consequences. While there are a variety of available pharmacotherapeutic approaches, information on new pathways is in high demand and the achievement of treatment goals is greatly desired. Therefore, targeting the RAS presents an interesting opportunity to better understand this process. This has been supported by preclinical studies, primarily based on RAS enzyme, receptor-inhibition, and selective agonists, which are characterized by pleiotropic properties. Although there are some antiepileptic drugs (AEDs) that interfere with RAS, the main targeted therapy of this pathway contributes in synergy with AEDs. However, the RAS-targeted treatment alone, or in combination with AEDs, requires clinical studies to contribute to, and clarify, the evidence on epilepsy management. There is also a genetic association between RAS and epilepsy, and an involvement of pharmacogenetics in RAS, so there are possibilities for the development of new diagnostic and personalized treatments for epilepsy.

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

Cited by 38 publications

References 43 publications

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage

Mas Receptor Activation Attenuates Allergic Airway Inflammation via Inhibiting JNK/CCL2-induced Macrophage Recruitment

Role of the Angiotensin Pathway and its Target Therapy in Epilepsy Management

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