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  Involvement of GPR17 in neuronal fibre outgrowth

Braune, M., Scherf, N., Heine, C., Sygnecka, K., Pillaiyar, T., Parravicini, C., et al. (2021). Involvement of GPR17 in neuronal fibre outgrowth. International Journal of Molecular Sciences, 22(21): 11683. doi:10.3390/ijms222111683.

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 Creators:
Braune, Max1, Author
Scherf, Nico2, Author              
Heine, Claudia1, Author
Sygnecka, Katja1, Author
Pillaiyar, Thanigaimalai3, Author
Parravicini, Chiara4, Author
Heimrich, Bernd5, Author
Abbracchio, Maria P.4, Author
Müller, Christa E.3, Author
Franke, Heike1, Author
Affiliations:
1Rudolf-Boehm-Institute of Pharmacology and Toxicology, Leipzig, Germany, ou_persistent22              
2Method and Development Group Neural Data Science and Statistical Computing, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_3282987              
3Department of Pharmaceutical & Medicinal Chemistry, University Bonn, Germany, ou_persistent22              
4Faculty of Pharmacy, University of Milan, Italy, ou_persistent22              
5Center for Basics in NeuroModulation (NeuroModulBasics), Albert Ludwigs University Freiburg, Germany, ou_persistent22              

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Free keywords: G protein-coupled receptor 17 (GPR17); NG2; Ex vivo organotypic brain slice co-culture; Montelukast; Neurite outgrowth; Neurodegeneration and neuroregeneration
 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.

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Language(s): eng - English
 Dates: 2021-10-242021-10-042021-10-242021-10-28
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.3390/ijms222111683
PMID: 34769111
PMC: PMC8584086
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Title: International Journal of Molecular Sciences
  Abbreviation : Int. J. Mol. Sci.
Source Genre: Journal
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Publ. Info: Basel, Switzerland : MDPI AG
Pages: - Volume / Issue: 22 (21) Sequence Number: 11683 Start / End Page: - Identifier: ISSN: 1422-0067
CoNE: https://pure.mpg.de/cone/journals/resource/1422-0067