Involvement of GPR17 in neuronal fibre outgrowth
Abstract: 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 growth-promoting 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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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International journal of molecular sciences. - 22, 21 (2021) , 11683, ISSN: 1422-0067
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2021
- Creator
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Braune, Max
Scherf, Nico
Heine, Claudia
Sygnecka, Katja
Pillaiyar, Thanigaimalai
Parravicini, Chiara
Heimrich, Bernd
Abbracchio, Maria Pia
Müller, Christa E.
Franke, Heike
- DOI
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10.3390/ijms222111683
- URN
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urn:nbn:de:bsz:25-freidok-2226198
- Rights
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Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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15.08.2025, 7:34 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- Braune, Max
- Scherf, Nico
- Heine, Claudia
- Sygnecka, Katja
- Pillaiyar, Thanigaimalai
- Parravicini, Chiara
- Heimrich, Bernd
- Abbracchio, Maria Pia
- Müller, Christa E.
- Franke, Heike
- Universität
Time of origin
- 2021