Involvement of GPR17 in Neuronal Fibre Outgrowth

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 <i<ex v...
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Autor*in:	Max Braune [verfasserIn] Nico Scherf [verfasserIn] Claudia Heine [verfasserIn] Katja Sygnecka [verfasserIn] Thanigaimalai Pillaiyar [verfasserIn] Chiara Parravicini [verfasserIn] Bernd Heimrich [verfasserIn] Maria P. Abbracchio [verfasserIn] Christa E. Müller [verfasserIn] Heike Franke [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Schlagwörter:	G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 neurodegeneration and neuroregeneration

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 22(2021), 21, p 11683
Übergeordnetes Werk:	volume:22 ; year:2021 ; number:21, p 11683

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms222111683

Katalog-ID:	DOAJ050992864

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allfields	10.3390/ijms222111683 doi (DE-627)DOAJ050992864 (DE-599)DOAJf02a609b008746deb0d3c435e46d1e1c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Max Braune verfasserin aut Involvement of GPR17 in Neuronal Fibre Outgrowth 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<ex vivo</i< 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. G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) Chemistry Nico Scherf verfasserin aut Claudia Heine verfasserin aut Katja Sygnecka verfasserin aut Thanigaimalai Pillaiyar verfasserin aut Chiara Parravicini verfasserin aut Bernd Heimrich verfasserin aut Maria P. Abbracchio verfasserin aut Christa E. Müller verfasserin aut Heike Franke verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 21, p 11683 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:21, p 11683 https://doi.org/10.3390/ijms222111683 kostenfrei https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c kostenfrei https://www.mdpi.com/1422-0067/22/21/11683 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 21, p 11683
spelling	10.3390/ijms222111683 doi (DE-627)DOAJ050992864 (DE-599)DOAJf02a609b008746deb0d3c435e46d1e1c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Max Braune verfasserin aut Involvement of GPR17 in Neuronal Fibre Outgrowth 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<ex vivo</i< 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. G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) Chemistry Nico Scherf verfasserin aut Claudia Heine verfasserin aut Katja Sygnecka verfasserin aut Thanigaimalai Pillaiyar verfasserin aut Chiara Parravicini verfasserin aut Bernd Heimrich verfasserin aut Maria P. Abbracchio verfasserin aut Christa E. Müller verfasserin aut Heike Franke verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 21, p 11683 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:21, p 11683 https://doi.org/10.3390/ijms222111683 kostenfrei https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c kostenfrei https://www.mdpi.com/1422-0067/22/21/11683 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 21, p 11683
allfields_unstemmed	10.3390/ijms222111683 doi (DE-627)DOAJ050992864 (DE-599)DOAJf02a609b008746deb0d3c435e46d1e1c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Max Braune verfasserin aut Involvement of GPR17 in Neuronal Fibre Outgrowth 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<ex vivo</i< 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. G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) Chemistry Nico Scherf verfasserin aut Claudia Heine verfasserin aut Katja Sygnecka verfasserin aut Thanigaimalai Pillaiyar verfasserin aut Chiara Parravicini verfasserin aut Bernd Heimrich verfasserin aut Maria P. Abbracchio verfasserin aut Christa E. Müller verfasserin aut Heike Franke verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 21, p 11683 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:21, p 11683 https://doi.org/10.3390/ijms222111683 kostenfrei https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c kostenfrei https://www.mdpi.com/1422-0067/22/21/11683 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 21, p 11683
allfieldsGer	10.3390/ijms222111683 doi (DE-627)DOAJ050992864 (DE-599)DOAJf02a609b008746deb0d3c435e46d1e1c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Max Braune verfasserin aut Involvement of GPR17 in Neuronal Fibre Outgrowth 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<ex vivo</i< 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. G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) Chemistry Nico Scherf verfasserin aut Claudia Heine verfasserin aut Katja Sygnecka verfasserin aut Thanigaimalai Pillaiyar verfasserin aut Chiara Parravicini verfasserin aut Bernd Heimrich verfasserin aut Maria P. Abbracchio verfasserin aut Christa E. Müller verfasserin aut Heike Franke verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 21, p 11683 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:21, p 11683 https://doi.org/10.3390/ijms222111683 kostenfrei https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c kostenfrei https://www.mdpi.com/1422-0067/22/21/11683 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 21, p 11683
allfieldsSound	10.3390/ijms222111683 doi (DE-627)DOAJ050992864 (DE-599)DOAJf02a609b008746deb0d3c435e46d1e1c DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Max Braune verfasserin aut Involvement of GPR17 in Neuronal Fibre Outgrowth 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 <i<ex vivo</i< 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. G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) Chemistry Nico Scherf verfasserin aut Claudia Heine verfasserin aut Katja Sygnecka verfasserin aut Thanigaimalai Pillaiyar verfasserin aut Chiara Parravicini verfasserin aut Bernd Heimrich verfasserin aut Maria P. Abbracchio verfasserin aut Christa E. Müller verfasserin aut Heike Franke verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 22(2021), 21, p 11683 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:22 year:2021 number:21, p 11683 https://doi.org/10.3390/ijms222111683 kostenfrei https://doaj.org/article/f02a609b008746deb0d3c435e46d1e1c kostenfrei https://www.mdpi.com/1422-0067/22/21/11683 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2021 21, p 11683
language	English
source	In International Journal of Molecular Sciences 22(2021), 21, p 11683 volume:22 year:2021 number:21, p 11683
sourceStr	In International Journal of Molecular Sciences 22(2021), 21, p 11683 volume:22 year:2021 number:21, p 11683
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration Biology (General) Chemistry
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container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Max Braune @@aut@@ Nico Scherf @@aut@@ Claudia Heine @@aut@@ Katja Sygnecka @@aut@@ Thanigaimalai Pillaiyar @@aut@@ Chiara Parravicini @@aut@@ Bernd Heimrich @@aut@@ Maria P. Abbracchio @@aut@@ Christa E. Müller @@aut@@ Heike Franke @@aut@@
publishDateDaySort_date	2021-01-01T00:00:00Z
hierarchy_top_id	316340715
id	DOAJ050992864
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callnumber-first	Q - Science
author	Max Braune
spellingShingle	Max Braune misc QH301-705.5 misc QD1-999 misc G protein-coupled receptor 17 (GPR17) misc neurite outgrowth misc montelukast misc NG2 misc <i<ex vivo</i< organotypic brain slice co-culture misc neurodegeneration and neuroregeneration misc Biology (General) misc Chemistry Involvement of GPR17 in Neuronal Fibre Outgrowth
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topic_title	QH301-705.5 QD1-999 Involvement of GPR17 in Neuronal Fibre Outgrowth G protein-coupled receptor 17 (GPR17) neurite outgrowth montelukast NG2 <i<ex vivo</i< organotypic brain slice co-culture neurodegeneration and neuroregeneration
topic	misc QH301-705.5 misc QD1-999 misc G protein-coupled receptor 17 (GPR17) misc neurite outgrowth misc montelukast misc NG2 misc <i<ex vivo</i< organotypic brain slice co-culture misc neurodegeneration and neuroregeneration misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc G protein-coupled receptor 17 (GPR17) misc neurite outgrowth misc montelukast misc NG2 misc <i<ex vivo</i< organotypic brain slice co-culture misc neurodegeneration and neuroregeneration misc Biology (General) misc Chemistry
topic_browse	misc QH301-705.5 misc QD1-999 misc G protein-coupled receptor 17 (GPR17) misc neurite outgrowth misc montelukast misc NG2 misc <i<ex vivo</i< organotypic brain slice co-culture misc neurodegeneration and neuroregeneration misc Biology (General) misc Chemistry
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title	Involvement of GPR17 in Neuronal Fibre Outgrowth
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title_full	Involvement of GPR17 in Neuronal Fibre Outgrowth
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author_browse	Max Braune Nico Scherf Claudia Heine Katja Sygnecka Thanigaimalai Pillaiyar Chiara Parravicini Bernd Heimrich Maria P. Abbracchio Christa E. Müller Heike Franke
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doi_str_mv	10.3390/ijms222111683
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title_sort	involvement of gpr17 in neuronal fibre outgrowth
callnumber	QH301-705.5
title_auth	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 <i<ex vivo</i< 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.
abstractGer	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 <i<ex vivo</i< 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.
abstract_unstemmed	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 <i<ex vivo</i< 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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container_issue	21, p 11683
title_short	Involvement of GPR17 in Neuronal Fibre Outgrowth
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score	7.4021063

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Involvement of GPR17 in Neuronal Fibre Outgrowth

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Zugang & Verfügbarkeit

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