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,...
| Authors: | ; ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2024 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/218496 |
| Online Access: | https://hdl.handle.net/2445/218496 |
| Access Level: | Open access |
| Keyword: | Cànnabis Esclerosi múltiple Escorça frontal Cannabis Multiple sclerosis Prefrontal cortex |
| _version_ | 1878730777398607872 |
|---|---|
| author | Menéndez-Pérez, Carlota |
| 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 |
| author_browse | Franco Fernández, Rafael Martínez-Pinilla, Eva Menéndez-Pérez, Carlota Navarro, Ana Rivas‐Santisteban, Rafael Tolivia, Jorge del Valle, Eva |
| author_facet | Menéndez-Pérez, Carlota Rivas‐Santisteban, Rafael del Valle, Eva Tolivia, Jorge Navarro, Ana Franco Fernández, Rafael Martínez-Pinilla, Eva |
| author_role | author |
| collection | Dipòsit Digital de la UB |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_232ff3b4e36cb63dd6f7a61d330c986d |
| institution | Universidad de Barcelona |
| instname_str | Universidad de Barcelona |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:diposit.ub.edu:2445/218496 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher | MDPI |
| publisherStr | MDPI |
| reponame_str | Dipòsit Digital de la UB |
| 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 |
| 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 |
| status_str | publishedVersion |
| 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 |
| 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_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_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 |
| topic | Cànnabis Esclerosi múltiple Escorça frontal Cannabis Multiple sclerosis Prefrontal cortex |
| topic_facet | Cànnabis Esclerosi múltiple Escorça frontal Cannabis Multiple sclerosis Prefrontal cortex |
| url | https://hdl.handle.net/2445/218496 |