NS-417, a Novel Compound with Neurotrophic-Like Effects |
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Authors: | Dagø Lone Peters Dan Meyer Morten Hartz Barbara Kruse Vibeke Drejer Jørgen Grønborg Mette |
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Affiliation: | (1) NeuroSearch, DK-2750 Ballerup, Denmark;(2) NsGene, DK-2750 Ballerup, Denmark;(3) Department of Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Denmark;(4) Odense University, DK-5000 Odense C, Denmark;(5) NeuroSearch, DK-2750 Ballerup, Denmark |
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Abstract: | NS-417 (5-(4-Chlorophenyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo[3.2-h]isoquinoline-2,3-dione-3-oxim hydrochloric acid salt) belongs to a new chemical series of compounds. NS-417 rescued differentiated PC12 cells from death induced by withdrawal of serum and nerve growth factor. Furthermore, NS-417 stimulated neurotrophic factor-induced neurite outgrowth in undifferentiated PC12 cells. In accordance with this observation, NS-417 potentiated NGF-induced signaling, such as activation of the extracellular signal-regulated kinases ERK1 and ERK2 and the Akt kinase. NS-417 also enhanced ERK activation induced by 10 minutes stimulation with NGF, bFGF or EGF in PC12 cells. In addition to the effect in PC12 cells, NS-417 increased the number of tyrosine hydroxylase (TH) positive cells in cultures established from dissociated E14 rat ventral mesencephali. |
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Keywords: | Neurotrophic neurites survival PC12 cells ERK activation primary dopaminergic cultures |
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