Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q

Robert Veerhuis, Ronald S. Boshuizen, Michela Morbin, Giulia Mazzoleni, J. J M Hoozemans, J. P M Langedijk, Fabrizio Tagliavini, J. P M Langeveld, Piet Eikelenboom

Research output: Contribution to journalArticlepeer-review

Abstract

Complement activation products C1q and C3d, serum amyloid P component (SAP) and activated glial cells accumulate in amyloid deposits of conformationally changed prion protein (PrPSc) in Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and scrapie-infected mouse brain. Biological properties, including the potential to activate microglia, relate to prion (PrP) peptide fibrillogenic abilities. We investigated if SAP and C1q influence the fibrillogenic properties of human and mouse PrP peptide and concomitantly their stimulatory effects on human microglia in vitro. PrP-peptide induced microglial IL-6 and TNF-α release significantly increased in the presence of SAP and C1q. Also, SAP and C1q enhanced PrP-peptide fibril formation as revealed by electron microscopy and thioflavin S-based quantitative assays. This suggests that SAP and C1q contribute to fibrillar state-dependent cellular effects of PrP. Combined, ultrastructural and thioflavin assays, together with microglial cytokine release measurements, provide a test system to screen potential, fibrillarity impeding therapeutics for prion disease.

Original languageEnglish
Pages (from-to)273-282
Number of pages10
JournalNeurobiology of Disease
Volume19
Issue number1-2
DOIs
Publication statusPublished - Jun 2005

Keywords

  • C1q
  • Creutzfeldt-Jakob disease (CJD)
  • Cytokines
  • Fibrillarity
  • Microglia
  • Prion peptides
  • SAP
  • Thioflavin

ASJC Scopus subject areas

  • Neurology

Fingerprint Dive into the research topics of 'Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q'. Together they form a unique fingerprint.

Cite this