Abstract
Alzheimer's disease (AD) is characterized by the presence of beta-amyloid (Abeta) protein deposits in the brain and increased Abeta (1-42) peptide production is thought to be one of the early events in the pathogenesis of AD that leads to progressive neurodegenerative processes and dementia. Using cDNA subtraction and reverse transcription-polymerase chain reaction, we examined the Abeta (1-42) peptide-induced gene expression in rat neuroblastoma B104 cells. In addition we hypothesized that interleukin-11 (IL-11) supports neuronal survival. We found that Abeta (1-42) activates L-phosphoserine phosphatase in neuronal cells which is inhibited by IL-11. Moreover, IL-11 inhibits Abeta (1-42)-induced neurotoxicity in a dose-dependent manner. Our study suggests that L-phosphoserine phosphatase may play a role in altered neuronal function in AD via enhancing glutamate-induced neurotoxicity by D-serine and the IL-11 receptor system may act as a neuroprotective cytokine in human brain.
MeSH terms
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Amyloid beta-Peptides / pharmacology*
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Animals
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Blotting, Southern
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Cell Survival / drug effects
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Dose-Response Relationship, Drug
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Gene Expression Regulation, Enzymologic / drug effects*
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Interleukin-11 / pharmacology*
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Nerve Degeneration / drug therapy
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Nerve Degeneration / metabolism
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Nerve Degeneration / prevention & control
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Neuroblastoma
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Neurons / cytology
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Neurons / drug effects
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Neurons / enzymology*
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Neuroprotective Agents / pharmacology
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Peptide Fragments / pharmacology*
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Phosphoric Monoester Hydrolases / genetics*
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Phosphoric Monoester Hydrolases / metabolism
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RNA, Messenger / analysis
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Rats
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Receptors, Interleukin / physiology
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Receptors, N-Methyl-D-Aspartate / physiology
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Serine / pharmacology
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Signal Transduction / drug effects
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Tumor Cells, Cultured
Substances
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Amyloid beta-Peptides
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Interleukin-11
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Neuroprotective Agents
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Peptide Fragments
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RNA, Messenger
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Receptors, Interleukin
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Receptors, N-Methyl-D-Aspartate
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amyloid beta-protein (1-42)
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Serine
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Phosphoric Monoester Hydrolases
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phosphoserine phosphatase