The anti-inflammatory Annexin A1 induces the clearance and degradation of the Amyloid-β peptide

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Title: The anti-inflammatory Annexin A1 induces the clearance and degradation of the Amyloid-β peptide
Author(s): Sastre, M
Ries, M
Loiola, R
Shah, UN
Gentleman, S
Solito, E
Item Type: Journal Article
Abstract: Background: The toxicity of amyloid-β (Aβ) peptide present in the brain of Alzheimer’s disease (AD) patients is thought to be mediated via the increased secretion of pro-inflammatory mediators, which can lead to neuronal dysfunction and cell death. In addition, we have previously shown that inflammation can affect Aβ generation. More recently, we have reported that in vitro administration of the anti-inflammatory mediator Annexin A1 (ANXA1) following an inflammatory challenge suppressed microglial activation and this effect was mediated through Formyl Peptide Receptor Like-1 (FPRL1/FPR2) signalling. The aim of this study was to determine the potential role of ANXA1 in the generation and clearance of Aβ. Methods: We first compared ANXA1 protein expression in the brains of AD patients and healthy controls as well as in the 5XFAD model of AD. To determine the role of ANXA1 in the processing of amyloid precursor protein (APP) and the degradation of Aβ, N2a neuroblastoma cells were treated with human recombinant ANXA1 or transfected with ANXA1 siRNA. We also investigated the effect of ANXA1 on Aβ phagocytosis and microglial activation in BV2 cells treated with synthetic Aβ. Results: Our data show that ANXA1 is increased in the brains of AD patients and animal models of AD at early stages. ANXA1 was able to reduce the levels of Aβ by increasing its enzymatic degradation by neprilysin in N2a cells and to stimulate Aβ phagocytosis by microglia. These effects were mediated through FPRL1 receptors. In addition, ANXA1 inhibited the Aβ-stimulated secretion of inflammatory mediators by microglia. Conclusions: These data suggest that ANXA1 plays a pivotal role in Aβ clearance and supports the use of ANXA1 as potential pharmacological tool for AD therapeutics.
Publication Date: 2-Sep-2016
Date of Acceptance: 10-Aug-2016
ISSN: 1742-2094
Publisher: BioMed Central
Journal / Book Title: Journal of Neuroinflammation
Volume: 13
Copyright Statement: © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Alzheimer's Research UK (ARUK)
Funder's Grant Number: TMTG1D8R
Medical Research Council
Keywords: Neurology & Neurosurgery
1103 Clinical Sciences
1109 Neurosciences
1107 Immunology
Publication Status: Published
Article Number: 234
Appears in Collections:Department of Medicine
Faculty of Medicine

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