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Forschungsdatenbank PMU-SQQUID

Inhibition of leukotriene receptors boosts neural progenitor proliferation.
Huber, C; Marschallinger, J; Tempfer, H; Furtner, T; Couillard-Despres, S; Bauer, HC; Rivera, FJ; Aigner, L;
Cell Physiol Biochem. 2011; 28(5):793-804
Originalarbeiten (Zeitschrift)

PMU-Autor/inn/en

Aigner Ludwig
Bauer Hans Christian
Couillard-Després Sébastien
Furtner Tanja
Marschallinger Julia
Rivera Gomez-Barris Francisco J.
Tempfer Herbert

Abstract

Neural stem and progenitor cells serve as a reservoir for new neurons in the adult brain throughout lifetime. One of the critical steps determining the net production of new neurons is neural progenitor proliferation, which needs to be tightly controlled. Since inflammation has detrimental effects on neurogenesis and the 5-lipoxygenase/leukotriene pathway is involved in inflammatory processes, we investigated the effects of leukotrienes and montelukast, a small molecule inhibitor of the leukotriene receptors CysLT(1)R and GPR17, on neural stem and progenitor cell proliferation. We demonstrate expression of the leukotriene receptor GPR17 by neural progenitors and by neural stem cells. Stimulation with excess amounts of leukotrienes did not affect progenitor proliferation, whereas blockade of GPR17 with montelukast strongly elevated neural stem and progenitor proliferation, while maintaining their differentiation fate and potential. This effect was associated with increased ERK1/2 phosphorylation suggesting an involvement of the EGF signaling cascade. Based on our results, montelukast and the inhibition of the 5-LOX pathway might be potent candidates for future therapies employing neurogenesis to promote structural and functional improvement in neurodegeneration, neuropsychiatric disease and ageing.


Useful keywords (using NLM MeSH Indexing)

Acetates/pharmacology

Animals

Cell Proliferation/drug effects

Female

Leukotriene Antagonists/pharmacology*

Leukotrienes/pharmacology

Mitogen-Activated Protein Kinase 1/metabolism

Mitogen-Activated Protein Kinase 3/metabolism

Neural Stem Cells/drug effects

Neural Stem Cells/metabolism*

Neurogenesis

Phosphorylation

Quinolines/pharmacology

Rats

Receptors, G-Protein-Coupled/metabolism

Receptors, Leukotriene/chemistry

Receptors, Leukotriene/metabolism*

Signal Transduction


Find related publications in this database (Keywords)

Neurogenesis
Neural progenitors
Differentiation
Leukotriene
MAP kinase pathway