Efficiency of ANXA1 shRNA infection in BV2 cells. Representative Western blot image showing protein expression of ANXA1 in BV2 cells infected with control shRNA, and ANXA1 shRNA—clones 492A, 492B, 495A and 495B. Band intensities were determined using ImageJ and normalised to tubulin. (PDF 99 kb

Egle Solito (390951)

Magdalena Sastre (3453974)

Miriam Ries (3453977)

Rodrigo Loiola (3453980)

Steve Gentleman (3453983)

Urvi Shah (83424)

Journal of Neuroinflammation

PubMed

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

Ries M.

Loiola R.

Shah U. N.

Gentleman S. M.

Solito E.

Sastre M.

Archivio della ricerca - Università degli studi di Napoli Federico II

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

This study was partially funded by the Imperial College Medical Research
Council Doctoral Training Centre (studentship to MR). RAL fellow was sponsored
from CAPES Foundation, Ministry of Education, Brazil (grant#7326/2014-09).
ES research is supported by FISM-Fondazione Italiana Sclerosi Multipla-cod
2014/R/2

Ries, M

Loiola, R

Shah, UN

Gentleman, SM

Solito, E

Sastre, M

Queen Mary Research Online

The anti-inflammatory Annexin A1 induces the clearance and degradation of the amyloid-beta peptide

Electronic Library Belinsky

Весь Тагил. 2011. № 006

Miriam Ries

Rodrigo Loiola

Urvi N. Shah

Steve M. Gentleman

Egle Solito

Magdalena Sastre

Crossref

English

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Additional file 1: Figure S1. of The anti-inflammatory Annexin A1 induces the clearance and degradation of the amyloid-β peptide

Springer - Publisher Connector

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

Gentleman, S

Spiral - Imperial College Digital Repository

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

file:///data/core-remote/dit/data/Springer-OA/pdf/ecc/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjExODYvczEyOTc0LTAxNi0wNjkyLTYucGRm.pdf

Весь Тагил. 2011. № 006

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Archivio della ricerca - Università degli studi di Napoli Federico II

Queen Mary Research Online

Electronic Library Belinsky

Crossref

FigShare

Springer - Publisher Connector

Spiral - Imperial College Digital Repository

Springer - Publisher Connector