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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid beta-Peptides / pharmacology
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Analysis of Variance
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Animals
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Animals, Newborn
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Cell Survival / drug effects
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Cells, Cultured
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Coculture Techniques / methods
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Enzyme-Linked Immunosorbent Assay / methods
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Inactivation, Metabolic
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Infections / therapy
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Lipopolysaccharides / pharmacology*
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Mice
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Microglia / drug effects*
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Microglia / physiology
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Neuroblastoma
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Neurons / cytology
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Neurons / drug effects*
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Peptide Fragments / pharmacology
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Peptides / pharmacology
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Prions / pharmacology*
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Tetrazolium Salts
Substances
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2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium
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Amyloid beta-Peptides
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Cytokines
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Lipopolysaccharides
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Peptide Fragments
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Peptides
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Prions
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Tetrazolium Salts
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amyloid beta-protein (1-40)