NR ASRS
AU Veerhuis,R.; Boshuizen,R.S.; Morbin,M.; Mazzoleni,G.; Hoozemans,J.J.M.; Langedijk,J.P.M.; Tagliavini,F.; Langeveld,J.P.M.; Eikelenboom,P.
TI Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q
QU Neurobiology of Disease 2005 Jun-Jul; 19(1-2): 273-82
PT journal article
AB 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-alpha 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.
MH Aged; Aged, 80 and over; Amino Acid Sequence; Animals; Comparative Study; Complement 1q/*pharmacology; Humans; Mice; Microglia/*metabolism/*pathology; Middle Aged; Molecular Sequence Data; Peptide Fragments/genetics/*pharmacology; PrPsc Proteins/genetics/*pharmacology; Research Support, Non-U.S. Gov't; Serum Amyloid P-Component/*pharmacology
AD Institute for Clinical and Experimental Neurosciences-VU (ICEN-VU), Department of Psychiatry, Vrije Universiteit University Medical Center, Amsterdam, The Netherlands. r.veerhuis@vumc.nl
SP englisch
PO USA