Article (Scientific journals)
Microglial activation depends on beta-amyloid conformation: role of the formylpeptide receptor 2
Heurtaux, Tony; Michelucci, Alessandro; Losciuto, Sophie et al.
2010In Journal of Neurochemistry, 114 (2), p. 576-586
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Abstract :
[en] Alzheimer's disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Abeta) complexes or senile plaques. Abeta peptide is firstly produced as monomers, readily aggregating to form multimeric complexes, of which the smallest aggregates are known to be the most neurotoxic. In AD patients, abundant reactive microglia migrate to and surround the Abeta plaques. Though it is well known that microglia are activated by Abeta, little is known about the peptide conformation and the signaling cascades responsible for this activation. In this study, we have stimulated murine microglia with different Abeta(1-42) forms, inducing an inflammatory state, which was peptide conformation-dependent. The lightest oligomeric forms induced a more violent inflammatory response, whereas the heaviest oligomers and the fibrillar conformation were less potent inducers. BocMLF, a formylpeptide chemotactic receptor 2 antagonist, decreased the oligomeric Abeta-induced inflammatory response. The Abeta-induced signal transduction was found to depend on phosphorylation mechanisms mediated by MAPKs and on activator protein 1/nuclear factor kappa-light-chain-enhancer of activated B cells pathways activation. These results suggest that the reactive microgliosis intensity during AD might depend on the disease progression and consequently on the Abeta conformation production. The recognition of Abeta by the formylpeptide chemotactic receptor 2 seems to be a starting point of the signaling cascade inducing an inflammatory state.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Heurtaux, Tony ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Michelucci, Alessandro ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Losciuto, Sophie ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Gallotti, Christian
Felten, Paul ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Dorban, Gauthier
Grandbarbe, Luc ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Morga, Eleonora 
Heuschling, Paul ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC)
Language :
English
Title :
Microglial activation depends on beta-amyloid conformation: role of the formylpeptide receptor 2
Publication date :
July 2010
Journal title :
Journal of Neurochemistry
ISSN :
1471-4159
Publisher :
Blackwell Science, Oxford, United Kingdom
Volume :
114
Issue :
2
Pages :
576-586
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 06 May 2013

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