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

R. Veerhuis; R.S. Boshuizen; M. Morbin; G. Mazzoleni; J.J. Hoozemans; J.P. Langedijk; F. Tagliavini; J.P.M. Langeveld; P. Eikelenboom

doi:10.1016/j.nbd.2005.01.005

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

R. Veerhuis, R.S. Boshuizen, M. Morbin, G. Mazzoleni, J.J. Hoozemans, J.P. Langedijk, F. Tagliavini, J.P.M. Langeveld, P. Eikelenboom

Research output: Contribution to journal › Article › Academic › peer-review

23 Citations (Scopus)

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-¿ 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 language	English
Pages (from-to)	273-282
Journal	Neurobiology of Disease
Volume	19
Issue number	1-2
DOIs	https://doi.org/10.1016/j.nbd.2005.01.005
Publication status	Published - 2005

Keywords

classical complement pathway
p component binds
in-vitro
alzheimers-disease
prostaglandin e-2
damaged neurons
murine scrapie
cytokines
neurotoxicity
fragment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.nbd.2005.01.005

TSE's (WOT-01-002-031, WOT-01-002-001.01)
van Keulen, L. (Project Leader)
1/01/08 → 31/12/24
Project: LVVN project

Cite this

Veerhuis, R., Boshuizen, R. S., Morbin, M., Mazzoleni, G., Hoozemans, J. J., Langedijk, J. P., Tagliavini, F., Langeveld, J. P. M., & Eikelenboom, P. (2005). Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q. Neurobiology of Disease, 19(1-2), 273-282. https://doi.org/10.1016/j.nbd.2005.01.005

@article{cfe8d73d98ce46fba1d98c92f55c19f4,

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

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¿Str{\"a}ussler¿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-¿ 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",

keywords = "classical complement pathway, p component binds, in-vitro, alzheimers-disease, prostaglandin e-2, damaged neurons, murine scrapie, cytokines, neurotoxicity, fragment",

author = "R. Veerhuis and R.S. Boshuizen and M. Morbin and G. Mazzoleni and J.J. Hoozemans and J.P. Langedijk and F. Tagliavini and J.P.M. Langeveld and P. Eikelenboom",

year = "2005",

doi = "10.1016/j.nbd.2005.01.005",

language = "English",

volume = "19",

pages = "273--282",

journal = "Neurobiology of Disease",

issn = "0969-9961",

publisher = "Elsevier",

number = "1-2",

}

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, R.S.

AU - Morbin, M.

AU - Mazzoleni, G.

AU - Hoozemans, J.J.

AU - Langedijk, J.P.

AU - Tagliavini, F.

AU - Langeveld, J.P.M.

AU - Eikelenboom, P.

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¿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-¿ 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

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-¿ 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

KW - classical complement pathway

KW - p component binds

KW - in-vitro

KW - alzheimers-disease

KW - prostaglandin e-2

KW - damaged neurons

KW - murine scrapie

KW - cytokines

KW - neurotoxicity

KW - fragment

U2 - 10.1016/j.nbd.2005.01.005

DO - 10.1016/j.nbd.2005.01.005

M3 - Article

SN - 0969-9961

VL - 19

SP - 273

EP - 282

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 1-2

ER -

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

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Projects

TSE's (WOT-01-002-031, WOT-01-002-001.01)

Cite this