Microglial activation depends on beta-amyloid conformation: Role of the formylpeptide receptor 2

Tony Heurtaux*, Alessandro Michelucci, Sophie Losciuto, Christian Gallotti, Paul Felten, Gauthier Dorban, Luc Grandbarbe, Eleonora Morga, Paul Heuschling

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

47 Citations (Scopus)


Alzheimer's disease (AD) is characterized by the presence of extracellular deposits referred to beta-amyloid (Aβ) complexes or senile plaques. Aβ 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 Aβ plaques. Though it is well known that microglia are activated by Aβ, 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 Aβ(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 Aβ-induced inflammatory response. The Aβ-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 Aβ conformation production. The recognition of Aβ by the formylpeptide chemotactic receptor 2 seems to be a starting point of the signaling cascade inducing an inflammatory state.

Original languageEnglish
Pages (from-to)576-586
Number of pages11
JournalJournal of Neurochemistry
Issue number2
Publication statusPublished - Jul 2010
Externally publishedYes


  • Alzheimer's disease
  • beta-amyloid
  • brain
  • immune cells
  • inflammation


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