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Published on: November 19, 2010
Detoxified lipopolysaccharide reduces microglial cell killing of prion-infected neurons
1Department of Veterinary Pathology, Glasgow University Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. c.bate@vet.gla.ac.uk
Abstract:
In vitro studies show that microglial cells kill neurons treated with the synthetic miniprion (sPrP106) or with amyloid-beta1-42 (a neurotoxic peptide found in Alzheimer's disease) by a process requiring the CD14 protein. The killing of treated primary cortical neurons by microglial cells was reduced by the addition of detoxified lipopolysaccharide (LPS), a deacylated form of LPS. Detoxified LPS also increased the survival of prion-infected neuroblastoma cells incubated with microglial cells. The presence of detoxified LPS reduced cytokine production in these co-cultures, and from isolated microglial cells incubated with native LPS, or fibrils of sPrP106 or amyloid-beta1-42. These results suggest that some compounds that bind to CD14 might reduce microglial cell activation and increase neuronal survival in prion and Alzheimer's diseases.
Insights
Microglial cells harm neurons in prion and Alzheimer's diseases. Compounds binding to CD14 may reduce microglial activation, protecting neurons and lowering harmful cytokine production.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglial cells are key immune cells in the brain.
- Prion diseases and Alzheimer's disease involve neuronal damage.
- CD14 protein is implicated in microglial activation.
Purpose of the Study:
- To investigate the role of CD14 in microglial-mediated neurotoxicity.
- To explore potential therapeutic strategies for prion and Alzheimer's diseases.
Main Methods:
- In vitro studies using primary cortical neurons and neuroblastoma cells.
- Co-culture systems with microglial cells.
- Treatment with synthetic miniprion (sPrP106) and amyloid-beta1-42.
- Addition of detoxified lipopolysaccharide (LPS).
- Measurement of cytokine production.
Main Results:
- Microglial cells kill neurons treated with sPrP106 or amyloid-beta1-42 via a CD14-dependent process.
- Detoxified LPS reduced microglial-mediated neurotoxicity and increased neuronal survival.
- Detoxified LPS decreased pro-inflammatory cytokine production.
Conclusions:
- CD14 is crucial for microglial activation leading to neurotoxicity.
- Compounds targeting CD14 may offer a therapeutic approach for prion and Alzheimer's diseases.
- Modulating CD14 could reduce neuroinflammation and preserve neuronal function.
