TY - JOUR
T1 - Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q
AU - Veerhuis, R
AU - Boshuizen, RS
AU - Morbin, M.
AU - Mazzoleni, G
AU - Hoozemans, JJM
AU - Langedijk, JPM
AU - Tagliavini, F.
AU - Langeveld, JPM
AU - Eikelenboom, P
AU - Boshuizen, Ronald S.
AU - Langedijk, Johannes P. M.
AU - Langeveld, Jan P. M.
PY - 2005
Y1 - 2005
N2 - 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-Straussier-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. (c) 2005 Elsevier Inc. All rights reserved
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-Straussier-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. (c) 2005 Elsevier Inc. All rights reserved
KW - C1q
KW - Creutzfeldt Jakob disease (CJD)
KW - SAP
KW - cytokines
KW - fibrillarity
KW - microglia
KW - prion peptides
KW - thioflavin
U2 - https://doi.org/10.1016/j.nbd.2005.01.005
DO - https://doi.org/10.1016/j.nbd.2005.01.005
M3 - Article
C2 - 15837583
SN - 0969-9961
VL - 19
SP - 273
EP - 282
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 1-2
ER -