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Braune, Max [VerfasserIn]; Scherf, Nico [VerfasserIn]; Heine, Claudia [VerfasserIn]; Sygnecka, Katja [VerfasserIn]; Pillaiyar, Thanigaimalai [VerfasserIn]; Parravicini, Chiara [VerfasserIn]; Heimrich, Bernd [VerfasserIn]; Abbracchio, Maria P. [VerfasserIn]; Müller, Christa E. [VerfasserIn]; Franke, Heike [VerfasserIn]

Involvement of GPR17 in Neuronal Fibre Outgrowth

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  • Medientyp: E-Artikel
  • Titel: Involvement of GPR17 in Neuronal Fibre Outgrowth
  • Beteiligte: Braune, Max [VerfasserIn]; Scherf, Nico [VerfasserIn]; Heine, Claudia [VerfasserIn]; Sygnecka, Katja [VerfasserIn]; Pillaiyar, Thanigaimalai [VerfasserIn]; Parravicini, Chiara [VerfasserIn]; Heimrich, Bernd [VerfasserIn]; Abbracchio, Maria P. [VerfasserIn]; Müller, Christa E. [VerfasserIn]; Franke, Heike [VerfasserIn]
  • Erschienen: Basel : MDPI, [2024]
  • Sprache: Englisch
  • Schlagwörter: G protein-coupled receptor 17 (GPR17); neurite outgrowth; montelukast; NG2; ex vivo organotypic brain slice co-culture; neurodegeneration and neuroregeneration ; Medizin ; medicine
  • Entstehung:
  • Anmerkungen: Hinweis: Link zur Erstveröffentlichung URL: https://doi.org/ 10.3390/ijms222111683
  • Beschreibung: Characterization of new pharmacological targets is a promising approach in research of neurorepair mechanisms. The G protein-coupled receptor 17 (GPR17) has recently been proposed as an interesting pharmacological target, e.g., in neuroregenerative processes. Using the well-established ex vivo model of organotypic slice co-cultures of the mesocortical dopaminergic system (prefrontal cortex (PFC) and substantia nigra/ventral tegmental area (SN/VTA) complex), the influence of GPR17 ligands on neurite outgrowth from SN/VTA to the PFC was investigated. The growthpromoting effects of Montelukast (MTK; GPR17- and cysteinyl-leukotriene receptor antagonist), the glial cell line-derived neurotrophic factor (GDNF) and of two potent, selective GPR17 agonists (PSB-16484 and PSB-16282) were characterized. Treatment with MTK resulted in a significant increase in mean neurite density, comparable with the effects of GDNF. The combination of MTK and GPR17 agonist PSB-16484 significantly inhibited neuronal growth. qPCR studies revealed an MTK-induced elevated mRNA-expression of genes relevant for neuronal growth. Immunofluorescence labelling showed a marked expression of GPR17 on NG2-positive glia. Western blot and RT-qPCR analysis of untreated cultures suggest a time-dependent, injury-induced stimulation of GPR17. In conclusion, MTK was identified as a stimulator of neurite fibre outgrowth, mediating its effects through GPR17, highlighting GPR17 as an interesting therapeutic target in neuronal regeneration.
  • Zugangsstatus: Freier Zugang
  • Rechte-/Nutzungshinweise: Namensnennung (CC BY)