Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease

Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potenti...
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Autor*in:	Martínez-Pinilla, Eva [verfasserIn] Aguinaga, David [verfasserIn] Navarro, Gemma [verfasserIn] Rico, Alberto J. [verfasserIn] Oyarzábal, Julen [verfasserIn] Sánchez-Arias, Juan A. [verfasserIn] Lanciego, José Luis [verfasserIn] Franco, Rafael [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Cannabinoid receptors GPCRs Neurodegenerative diseases Neuroprotection MPP

Übergeordnetes Werk:	Enthalten in: Molecular neurobiology - Totowa, NJ : Humana Press, 1987, 56(2019), 8 vom: 28. Jan., Seite 5900-5910
Übergeordnetes Werk:	volume:56 ; year:2019 ; number:8 ; day:28 ; month:01 ; pages:5900-5910

Links:	Volltext

DOI / URN:	10.1007/s12035-019-1495-4

Katalog-ID:	SPR023988479

Internformat


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520			\|a Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.
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700	1		\|a Aguinaga, David \|e verfasserin \|4 aut
700	1		\|a Navarro, Gemma \|e verfasserin \|4 aut
700	1		\|a Rico, Alberto J. \|e verfasserin \|4 aut
700	1		\|a Oyarzábal, Julen \|e verfasserin \|4 aut
700	1		\|a Sánchez-Arias, Juan A. \|e verfasserin \|4 aut
700	1		\|a Lanciego, José Luis \|e verfasserin \|4 aut
700	1		\|a Franco, Rafael \|e verfasserin \|4 aut
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Indexfelder

author_variant	e m p emp d a da g n gn a j r aj ajr j o jo j a s a jas jasa j l l jl jll r f rf
matchkey_str	article:15591182:2019----::agtnc_adp5edcnaiodeetraaoetanuortciep
hierarchy_sort_str	2019
bklnumber	44.90
publishDate	2019
allfields	10.1007/s12035-019-1495-4 doi (DE-627)SPR023988479 (SPR)s12035-019-1495-4-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Martínez-Pinilla, Eva verfasserin aut Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection. Cannabinoid receptors (dpeaa)DE-He213 GPCRs (dpeaa)DE-He213 Neurodegenerative diseases (dpeaa)DE-He213 Neuroprotection (dpeaa)DE-He213 MPP (dpeaa)DE-He213 Aguinaga, David verfasserin aut Navarro, Gemma verfasserin aut Rico, Alberto J. verfasserin aut Oyarzábal, Julen verfasserin aut Sánchez-Arias, Juan A. verfasserin aut Lanciego, José Luis verfasserin aut Franco, Rafael verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2019), 8 vom: 28. Jan., Seite 5900-5910 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910 https://dx.doi.org/10.1007/s12035-019-1495-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2019 8 28 01 5900-5910
spelling	10.1007/s12035-019-1495-4 doi (DE-627)SPR023988479 (SPR)s12035-019-1495-4-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Martínez-Pinilla, Eva verfasserin aut Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection. Cannabinoid receptors (dpeaa)DE-He213 GPCRs (dpeaa)DE-He213 Neurodegenerative diseases (dpeaa)DE-He213 Neuroprotection (dpeaa)DE-He213 MPP (dpeaa)DE-He213 Aguinaga, David verfasserin aut Navarro, Gemma verfasserin aut Rico, Alberto J. verfasserin aut Oyarzábal, Julen verfasserin aut Sánchez-Arias, Juan A. verfasserin aut Lanciego, José Luis verfasserin aut Franco, Rafael verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2019), 8 vom: 28. Jan., Seite 5900-5910 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910 https://dx.doi.org/10.1007/s12035-019-1495-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2019 8 28 01 5900-5910
allfields_unstemmed	10.1007/s12035-019-1495-4 doi (DE-627)SPR023988479 (SPR)s12035-019-1495-4-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Martínez-Pinilla, Eva verfasserin aut Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection. Cannabinoid receptors (dpeaa)DE-He213 GPCRs (dpeaa)DE-He213 Neurodegenerative diseases (dpeaa)DE-He213 Neuroprotection (dpeaa)DE-He213 MPP (dpeaa)DE-He213 Aguinaga, David verfasserin aut Navarro, Gemma verfasserin aut Rico, Alberto J. verfasserin aut Oyarzábal, Julen verfasserin aut Sánchez-Arias, Juan A. verfasserin aut Lanciego, José Luis verfasserin aut Franco, Rafael verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2019), 8 vom: 28. Jan., Seite 5900-5910 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910 https://dx.doi.org/10.1007/s12035-019-1495-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2019 8 28 01 5900-5910
allfieldsGer	10.1007/s12035-019-1495-4 doi (DE-627)SPR023988479 (SPR)s12035-019-1495-4-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Martínez-Pinilla, Eva verfasserin aut Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection. Cannabinoid receptors (dpeaa)DE-He213 GPCRs (dpeaa)DE-He213 Neurodegenerative diseases (dpeaa)DE-He213 Neuroprotection (dpeaa)DE-He213 MPP (dpeaa)DE-He213 Aguinaga, David verfasserin aut Navarro, Gemma verfasserin aut Rico, Alberto J. verfasserin aut Oyarzábal, Julen verfasserin aut Sánchez-Arias, Juan A. verfasserin aut Lanciego, José Luis verfasserin aut Franco, Rafael verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2019), 8 vom: 28. Jan., Seite 5900-5910 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910 https://dx.doi.org/10.1007/s12035-019-1495-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2019 8 28 01 5900-5910
allfieldsSound	10.1007/s12035-019-1495-4 doi (DE-627)SPR023988479 (SPR)s12035-019-1495-4-e DE-627 ger DE-627 rakwb eng 610 570 ASE 44.90 bkl Martínez-Pinilla, Eva verfasserin aut Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection. Cannabinoid receptors (dpeaa)DE-He213 GPCRs (dpeaa)DE-He213 Neurodegenerative diseases (dpeaa)DE-He213 Neuroprotection (dpeaa)DE-He213 MPP (dpeaa)DE-He213 Aguinaga, David verfasserin aut Navarro, Gemma verfasserin aut Rico, Alberto J. verfasserin aut Oyarzábal, Julen verfasserin aut Sánchez-Arias, Juan A. verfasserin aut Lanciego, José Luis verfasserin aut Franco, Rafael verfasserin aut Enthalten in Molecular neurobiology Totowa, NJ : Humana Press, 1987 56(2019), 8 vom: 28. Jan., Seite 5900-5910 (DE-627)34858444X (DE-600)2079384-4 1559-1182 nnns volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910 https://dx.doi.org/10.1007/s12035-019-1495-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 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_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 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_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.90 ASE AR 56 2019 8 28 01 5900-5910
language	English
source	Enthalten in Molecular neurobiology 56(2019), 8 vom: 28. Jan., Seite 5900-5910 volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910
sourceStr	Enthalten in Molecular neurobiology 56(2019), 8 vom: 28. Jan., Seite 5900-5910 volume:56 year:2019 number:8 day:28 month:01 pages:5900-5910
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Cannabinoid receptors GPCRs Neurodegenerative diseases Neuroprotection MPP
dewey-raw	610
isfreeaccess_bool	false
container_title	Molecular neurobiology
authorswithroles_txt_mv	Martínez-Pinilla, Eva @@aut@@ Aguinaga, David @@aut@@ Navarro, Gemma @@aut@@ Rico, Alberto J. @@aut@@ Oyarzábal, Julen @@aut@@ Sánchez-Arias, Juan A. @@aut@@ Lanciego, José Luis @@aut@@ Franco, Rafael @@aut@@
publishDateDaySort_date	2019-01-28T00:00:00Z
hierarchy_top_id	34858444X
dewey-sort	3610
id	SPR023988479
language_de	englisch
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author	Martínez-Pinilla, Eva
spellingShingle	Martínez-Pinilla, Eva ddc 610 bkl 44.90 misc Cannabinoid receptors misc GPCRs misc Neurodegenerative diseases misc Neuroprotection misc MPP Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease
authorStr	Martínez-Pinilla, Eva
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topic_title	610 570 ASE 44.90 bkl Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease Cannabinoid receptors (dpeaa)DE-He213 GPCRs (dpeaa)DE-He213 Neurodegenerative diseases (dpeaa)DE-He213 Neuroprotection (dpeaa)DE-He213 MPP (dpeaa)DE-He213
topic	ddc 610 bkl 44.90 misc Cannabinoid receptors misc GPCRs misc Neurodegenerative diseases misc Neuroprotection misc MPP
topic_unstemmed	ddc 610 bkl 44.90 misc Cannabinoid receptors misc GPCRs misc Neurodegenerative diseases misc Neuroprotection misc MPP
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title	Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease
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title_full	Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease
author_sort	Martínez-Pinilla, Eva
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author_browse	Martínez-Pinilla, Eva Aguinaga, David Navarro, Gemma Rico, Alberto J. Oyarzábal, Julen Sánchez-Arias, Juan A. Lanciego, José Luis Franco, Rafael
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title_sort	targeting $ cb_{1} $ and gpr55 endocannabinoid receptors as a potential neuroprotective approach for parkinson’s disease
title_auth	Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease
abstract	Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.
abstractGer	Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.
abstract_unstemmed	Abstract Cannabinoid $ CB_{1} $ receptors ($ CB_{1} $R) and the GPR55 receptor are expressed in striatum and are potential targets in the therapy of Parkinson’s disease (PD), one of the most prevalent neurodegenerative diseases in developed countries. The aim of this paper was to address the potential of ligands acting on those receptors to prevent the action of a neurotoxic agent, $ MPP^{+} $, that specifically affects neurons of the substantia nigra due to uptake via the dopamine DAT transporter. The SH-SY5Y cell line model was used as it expresses DAT and, therefore, is able to uptake $ MPP^{+} $ that inhibits complex I of the respiratory mitochondrial chain and leads to cell death. Cells were transfected with cDNAs coding for either or both receptors. Receptors in cotransfected cells formed heteromers as indicated by the in situ proximity ligation assays. Cell viability was assayed by oxygen rate consumption and by the bromide-based MTT method. Assays of neuroprotection using two concentrations of $ MPP^{+} $ showed that cells expressing receptor heteromers were more resistant to the toxic effect. After correction by effects on cell proliferation, the $ CB_{1} $R antagonist, SR141716, afforded an almost full neuroprotection in $ CB_{1} $R-expressing cells even when a selective agonist, ACEA, was present. In contrast, SR141716 was not effective in cells expressing $ CB_{1} $/GPR55 heteromeric complexes. In addition, an agonist of GPR55, CID1792197, did not enhance neuroprotection in GPR55-expressing cells. These results show that neurons expressing heteromers are more resistant to cell death but question the real usefulness of $ CB_{1} $R, GPR55, and their heteromers as targets to afford PD-related neuroprotection.
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container_issue	8
title_short	Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease
url	https://dx.doi.org/10.1007/s12035-019-1495-4
remote_bool	true
author2	Aguinaga, David Navarro, Gemma Rico, Alberto J. Oyarzábal, Julen Sánchez-Arias, Juan A. Lanciego, José Luis Franco, Rafael
author2Str	Aguinaga, David Navarro, Gemma Rico, Alberto J. Oyarzábal, Julen Sánchez-Arias, Juan A. Lanciego, José Luis Franco, Rafael
ppnlink	34858444X
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isOA_txt	false
hochschulschrift_bool	false
doi_str	10.1007/s12035-019-1495-4
up_date	2024-07-03T22:48:14.702Z
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Targeting $ CB_{1} $ and GPR55 Endocannabinoid Receptors as a Potential Neuroprotective Approach for Parkinson’s Disease

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