Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System
Cannabinoids have shown to exert their therapeutic actions through a variety of targets. These include not only the canonical cannabinoid receptors CB<sub>1</sub>R and CB<sub>2</sub>R but also related orphan G protein-coupled receptors (GPCRs), ligand-gated ion channels, tran...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-01-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/3/1001 |
| _version_ | 1797409421646626816 |
|---|---|
| author | Ana Lago-Fernandez Sara Zarzo-Arias Nadine Jagerovic Paula Morales |
| author_facet | Ana Lago-Fernandez Sara Zarzo-Arias Nadine Jagerovic Paula Morales |
| author_sort | Ana Lago-Fernandez |
| collection | DOAJ |
| description | Cannabinoids have shown to exert their therapeutic actions through a variety of targets. These include not only the canonical cannabinoid receptors CB<sub>1</sub>R and CB<sub>2</sub>R but also related orphan G protein-coupled receptors (GPCRs), ligand-gated ion channels, transient receptor potential (TRP) channels, metabolic enzymes, and nuclear receptors. In this review, we aim to summarize reported compounds exhibiting their therapeutic effects upon the modulation of CB<sub>1</sub>R and/or CB<sub>2</sub>R and the nuclear peroxisome proliferator-activated receptors (PPARs). Concomitant actions at CBRs and PPARα or PPARγ subtypes have shown to mediate antiobesity, analgesic, antitumoral, or neuroprotective properties of a variety of phytogenic, endogenous, and synthetic cannabinoids. The relevance of this multitargeting mechanism of action has been analyzed in the context of diverse pathologies. Synergistic effects triggered by combinatorial treatment with ligands that modulate the aforementioned targets have also been considered. This literature overview provides structural and pharmacological insights for the further development of dual cannabinoids for specific disorders. |
| first_indexed | 2024-03-09T04:14:23Z |
| format | Article |
| id | doaj.art-c8cee5daa483427ea113fc07bbbd89fb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:14:23Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c8cee5daa483427ea113fc07bbbd89fb2023-12-03T13:56:24ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223100110.3390/ijms22031001Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid SystemAna Lago-Fernandez0Sara Zarzo-Arias1Nadine Jagerovic2Paula Morales3Medicinal Chemistry Institute, Spanish Research Council, Juan de la Cierva 3, 28006 Madrid, SpainMedicinal Chemistry Institute, Spanish Research Council, Juan de la Cierva 3, 28006 Madrid, SpainMedicinal Chemistry Institute, Spanish Research Council, Juan de la Cierva 3, 28006 Madrid, SpainMedicinal Chemistry Institute, Spanish Research Council, Juan de la Cierva 3, 28006 Madrid, SpainCannabinoids have shown to exert their therapeutic actions through a variety of targets. These include not only the canonical cannabinoid receptors CB<sub>1</sub>R and CB<sub>2</sub>R but also related orphan G protein-coupled receptors (GPCRs), ligand-gated ion channels, transient receptor potential (TRP) channels, metabolic enzymes, and nuclear receptors. In this review, we aim to summarize reported compounds exhibiting their therapeutic effects upon the modulation of CB<sub>1</sub>R and/or CB<sub>2</sub>R and the nuclear peroxisome proliferator-activated receptors (PPARs). Concomitant actions at CBRs and PPARα or PPARγ subtypes have shown to mediate antiobesity, analgesic, antitumoral, or neuroprotective properties of a variety of phytogenic, endogenous, and synthetic cannabinoids. The relevance of this multitargeting mechanism of action has been analyzed in the context of diverse pathologies. Synergistic effects triggered by combinatorial treatment with ligands that modulate the aforementioned targets have also been considered. This literature overview provides structural and pharmacological insights for the further development of dual cannabinoids for specific disorders.https://www.mdpi.com/1422-0067/22/3/1001PPARcannabinoidsCB<sub>1</sub>RCB<sub>2</sub>RFAAHmultitarget |
| spellingShingle | Ana Lago-Fernandez Sara Zarzo-Arias Nadine Jagerovic Paula Morales Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System International Journal of Molecular Sciences PPAR cannabinoids CB<sub>1</sub>R CB<sub>2</sub>R FAAH multitarget |
| title | Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System |
| title_full | Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System |
| title_fullStr | Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System |
| title_full_unstemmed | Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System |
| title_short | Relevance of Peroxisome Proliferator Activated Receptors in Multitarget Paradigm Associated with the Endocannabinoid System |
| title_sort | relevance of peroxisome proliferator activated receptors in multitarget paradigm associated with the endocannabinoid system |
| topic | PPAR cannabinoids CB<sub>1</sub>R CB<sub>2</sub>R FAAH multitarget |
| url | https://www.mdpi.com/1422-0067/22/3/1001 |
| work_keys_str_mv | AT analagofernandez relevanceofperoxisomeproliferatoractivatedreceptorsinmultitargetparadigmassociatedwiththeendocannabinoidsystem AT sarazarzoarias relevanceofperoxisomeproliferatoractivatedreceptorsinmultitargetparadigmassociatedwiththeendocannabinoidsystem AT nadinejagerovic relevanceofperoxisomeproliferatoractivatedreceptorsinmultitargetparadigmassociatedwiththeendocannabinoidsystem AT paulamorales relevanceofperoxisomeproliferatoractivatedreceptorsinmultitargetparadigmassociatedwiththeendocannabinoidsystem |