CD36 Participates in PrP106–126-Induced Activation of Microglia
Open accessAbstract
Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP) fragment 106-126 (PrP(106-126)). We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126) in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126)-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb). The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126). The results showed that PrP(106-126) treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α), increased iNOS expression and nitric oxide (NO) production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126)-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126)-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126)-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126). Together, these results suggest that CD36 is involved in PrP(106-126)-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126) and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides and open perspectives for new therapeutic strategies for prion diseases by modulation of CD36 signaling.
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Aggregated prion peptides bind microglial SRs, causing uptake and/or neurotoxin production.
“Aggregated prion peptides also interact with microglial SRs, leading to uptake and/or neurotoxin production99.”
From Microglia in neurodegeneration (2018) · cites this paper as [99]
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- Authors
- Kouadir, M., Yang, L., Tan, R., Shi, F., Lu, Y., Zhang, S., Yin, X., Zhou, X., & Zhao, D.
- Affiliations
- China Agricultural University (CN)
- Corresponding author
- Zhao, Deming
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-01-26
- Volume
- 7
- Issue
- 1
- Pages
- e30756
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3266924
- OpenAlex
- W2051508950
- Cited by
- 34
- References
- 49
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 1 · 2015: 4 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 2.44
- Type
- journal article
- Language
- en
- Update notices
- correction (2012-02-29)
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (30972164, 30871854, 31001048)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- CD36, microglial activation, prion disease, scavenger receptor class B, neuroinflammation, inflammatory cytokines, NF-κB activation, caspase-1, nitric oxide, Fyn tyrosine kinase, Src family kinases, BV-2 cells
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Gene Expression Regulation, Peptide Fragments, Prions, RNA, Messenger, Cytokines, Rats, Wistar, Microglia, Inflammation Mediators, CD36 Antigens, Mice, Rats
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