Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients

Multiple sclerosis (MS) is an autoimmune, inflammatory, and neurodegenerative disease of the central nervous system for which there is no cure, making it necessary to search for new treatments. The endocannabinoid system (ECS) plays a very important neuromodulatory role in the CNS. In recent years,...

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Autores: Menéndez-Pérez, Carlota, Rivas‐Santisteban, Rafael, del Valle, Eva, Tolivia, Jorge, Navarro, Ana, Franco Fernández, Rafael, Martínez-Pinilla, Eva
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/218496
Acceso en línea:https://hdl.handle.net/2445/218496
Access Level:acceso abierto
Palabra clave:Cànnabis
Esclerosi múltiple
Escorça frontal
Cannabis
Multiple sclerosis
Prefrontal cortex
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spelling Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients Menéndez-Pérez, Carlota Rivas‐Santisteban, Rafael del Valle, Eva Tolivia, Jorge Navarro, Ana Franco Fernández, Rafael Martínez-Pinilla, Eva Cànnabis Esclerosi múltiple Escorça frontal Cannabis Multiple sclerosis Prefrontal cortex Multiple sclerosis (MS) is an autoimmune, inflammatory, and neurodegenerative disease of the central nervous system for which there is no cure, making it necessary to search for new treatments. The endocannabinoid system (ECS) plays a very important neuromodulatory role in the CNS. In recent years, the formation of heteromers containing cannabinoid receptors and their up/downregulation in some neurodegenerative diseases have been demonstrated. Despite the beneficial effects shown by some phytocannabinoids in MS, the role of the ECS in its pathophysiology is unknown. The main objective of this work was to identify heteromers of cell surface proteins receptive to cannabinoids, namely GPR55, CB1 and CB2 receptors, in brain samples from control subjects and MS patients, as well as determining their cellular localization, using In Situ Proximity Ligation Assays and immunohistochemical techniques. For the first time, CB1R-GPR55 and CB2R-GPR55 heteromers are identified in the prefrontal cortex of the human brain, more in the grey than in the white matter. Remarkably, the number of CB1R-GPR55 and CB2R-GPR55 complexes was found to be increased in MS patient samples. The results obtained open a promising avenue of research on the use of these receptor complexes as potential therapeutic targets for the disease. MDPI https://hdl.handle.net/2445/218496
title Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
spellingShingle Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
Menéndez-Pérez, Carlota
Cànnabis
Esclerosi múltiple
Escorça frontal
Cannabis
Multiple sclerosis
Prefrontal cortex
title_short Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
title_full Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
title_fullStr Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
title_full_unstemmed Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
title_sort Heteromers Formed by GPR55 and Either Cannabinoid CB<sub>1</sub> or CB<sub>2</sub> Receptors Are Upregulated in the Prefrontal Cortex of Multiple Sclerosis Patients
author Menéndez-Pérez, Carlota
author_facet Menéndez-Pérez, Carlota
Rivas‐Santisteban, Rafael
del Valle, Eva
Tolivia, Jorge
Navarro, Ana
Franco Fernández, Rafael
Martínez-Pinilla, Eva
author_role author
author2 Rivas‐Santisteban, Rafael
del Valle, Eva
Tolivia, Jorge
Navarro, Ana
Franco Fernández, Rafael
Martínez-Pinilla, Eva
author2_role author
author
author
author
author
author
topic Cànnabis
Esclerosi múltiple
Escorça frontal
Cannabis
Multiple sclerosis
Prefrontal cortex
topic_facet Cànnabis
Esclerosi múltiple
Escorça frontal
Cannabis
Multiple sclerosis
Prefrontal cortex
description Multiple sclerosis (MS) is an autoimmune, inflammatory, and neurodegenerative disease of the central nervous system for which there is no cure, making it necessary to search for new treatments. The endocannabinoid system (ECS) plays a very important neuromodulatory role in the CNS. In recent years, the formation of heteromers containing cannabinoid receptors and their up/downregulation in some neurodegenerative diseases have been demonstrated. Despite the beneficial effects shown by some phytocannabinoids in MS, the role of the ECS in its pathophysiology is unknown. The main objective of this work was to identify heteromers of cell surface proteins receptive to cannabinoids, namely GPR55, CB1 and CB2 receptors, in brain samples from control subjects and MS patients, as well as determining their cellular localization, using In Situ Proximity Ligation Assays and immunohistochemical techniques. For the first time, CB1R-GPR55 and CB2R-GPR55 heteromers are identified in the prefrontal cortex of the human brain, more in the grey than in the white matter. Remarkably, the number of CB1R-GPR55 and CB2R-GPR55 complexes was found to be increased in MS patient samples. The results obtained open a promising avenue of research on the use of these receptor complexes as potential therapeutic targets for the disease.
publishDate 2024
format article
status_str publishedVersion
url https://hdl.handle.net/2445/218496
eu_rights_str_mv openAccess
publisher MDPI
institution Universidad de Barcelona
collection Dipòsit Digital de la UB
reponame_str Dipòsit Digital de la UB
instname_str Universidad de Barcelona
_version_ 1878432451946086400
publishDateSort 2024
author_browse Franco Fernández, Rafael
Martínez-Pinilla, Eva
Menéndez-Pérez, Carlota
Navarro, Ana
Rivas‐Santisteban, Rafael
Tolivia, Jorge
del Valle, Eva
publisherStr MDPI
score 6,9303427