Induction of rat L-phosphoserine phosphatase by amyloid-beta (1-42) is inhibited by interleukin-11.

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.