Abstract
Peroxisome proliferator-activated receptors (PPARs) have long been known as mediators of several physiological functions, among which the best characterized are lipid metabolism, energy balance and anti-inflammation. Their rather large and promiscuous ligand binding site has been recently discovered to accommodate, among a plethora of lipid molecules and metabolic intermediates, endocannabinoids and their cognate compounds, specifically belonging to the Nacylethanolamine group. In fact, oleoylethanolamide, palmitoylethanolamide and probably anandamide bind with relatively high affinity to PPARs and have now been included among their endogenous ligands. Through activation of PPARs these molecules exert a variety of physiological processes. Particularly, both long-term effects via genomic mechanisms and rapid non-genomic actions have been described, which in several instances are opposite to those evoked by activation of “classical” surface cannabinoid receptors. In this review, we describe how these effects are relevant under diverse physiological and pathophysiological circumstances, such as lipid metabolism and feeding behaviour, neuroprotection and epilepsy, circadian rhythms, addiction and cognition. A picture is emerging where nuclear receptors are involved in anorexiant, anti-inflammatory, neuroprotective, anti-epileptic, wakefulness- and cognitive-enhancing, and anti-addicting properties of endocannabinoid-like molecules. Further studies are necessary to fully understand cellular mechanisms underlying the interactions between endocannabinoids and PPARs, but also between their surface and nuclear receptors, and to exploit their potential therapeutic applications.
Keywords: Endocannabinoids, peroxisome-proliferator-activated receptors, feeding, inflammation, neuroprotection, epilepsy, addiction, circadian rhythms
Current Medicinal Chemistry
Title: From Surface to Nuclear Receptors: The Endocannabinoid Family Extends its Assets
Volume: 17 Issue: 14
Author(s): M. Pistis and M. Melis
Affiliation:
Keywords: Endocannabinoids, peroxisome-proliferator-activated receptors, feeding, inflammation, neuroprotection, epilepsy, addiction, circadian rhythms
Abstract: Peroxisome proliferator-activated receptors (PPARs) have long been known as mediators of several physiological functions, among which the best characterized are lipid metabolism, energy balance and anti-inflammation. Their rather large and promiscuous ligand binding site has been recently discovered to accommodate, among a plethora of lipid molecules and metabolic intermediates, endocannabinoids and their cognate compounds, specifically belonging to the Nacylethanolamine group. In fact, oleoylethanolamide, palmitoylethanolamide and probably anandamide bind with relatively high affinity to PPARs and have now been included among their endogenous ligands. Through activation of PPARs these molecules exert a variety of physiological processes. Particularly, both long-term effects via genomic mechanisms and rapid non-genomic actions have been described, which in several instances are opposite to those evoked by activation of “classical” surface cannabinoid receptors. In this review, we describe how these effects are relevant under diverse physiological and pathophysiological circumstances, such as lipid metabolism and feeding behaviour, neuroprotection and epilepsy, circadian rhythms, addiction and cognition. A picture is emerging where nuclear receptors are involved in anorexiant, anti-inflammatory, neuroprotective, anti-epileptic, wakefulness- and cognitive-enhancing, and anti-addicting properties of endocannabinoid-like molecules. Further studies are necessary to fully understand cellular mechanisms underlying the interactions between endocannabinoids and PPARs, but also between their surface and nuclear receptors, and to exploit their potential therapeutic applications.
Export Options
About this article
Cite this article as:
Pistis M. and Melis M., From Surface to Nuclear Receptors: The Endocannabinoid Family Extends its Assets, Current Medicinal Chemistry 2010; 17 (14) . https://dx.doi.org/10.2174/092986710790980014
DOI https://dx.doi.org/10.2174/092986710790980014 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Derivatives of Deoxypodophyllotoxin Induce Apoptosis through Bcl-2/Bax Proteins Expression
Anti-Cancer Agents in Medicinal Chemistry EDITORIAL
Current Signal Transduction Therapy Subject Index To Volume 2
Current Rheumatology Reviews Interaction of Macrocyclic Lactones with the Multidrug Transporters: The Bases of the Pharmacokinetics of Lipid-Like Drugs
Current Drug Metabolism Understanding the Molecular Mechanisms of Betel miRNAs on Human Health
MicroRNA Pharmacological Treatment of Diabetic Peripheral Neuropathy: An Update
CNS & Neurological Disorders - Drug Targets Clinical, Immunological and Therapeutic Aspects of Autoimmune Encephalitis
Recent Patents on CNS Drug Discovery (Discontinued) Microglia Phenotype Diversity
CNS & Neurological Disorders - Drug Targets 1,2,4-Triazine Analogs as Novel Class of Therapeutic Agents
Mini-Reviews in Medicinal Chemistry The Role of Spiritual Health Experience with Intensity and Duration of Labor Pain While Childbearing and Postpartum
Current Women`s Health Reviews Pharmacological Intervention at Ionotropic Glutamate Receptor Complexes
Current Pharmaceutical Design Are Circulating Monocytes as Microglia Orthologues Appropriate Biomarker Targets for Neuronal Diseases? (Supplementry Table)
Central Nervous System Agents in Medicinal Chemistry Patterns of Gray and White Matter Changes in Individuals at Risk for Alzheimer’s Disease
Current Alzheimer Research Natural Products and their (Semi-)Synthetic Forms in the Treatment of Migraine: History and Current Status
Current Medicinal Chemistry Non-Selective Cation Channel Blockers: Potential Use in Nervous System Basic Research and Therapeutics
Mini-Reviews in Medicinal Chemistry Pharmacotherapy of Borderline Personality Disorder: A Systematic Review
Current Medicinal Chemistry Three-dimensional Modelling of the Voltage-gated Sodium Ion Channel from Anopheles gambiae Reveals Spatial Clustering of Evolutionarily Conserved Acidic Residues at the Extracellular Sites
Current Neuropharmacology Cellular Actions of Gabapentin and Related Compounds on Cultured Sensory Neurones
Current Neuropharmacology Targeted Blockade of TARP-γ8-Associated AMPA Receptors: Anticonvulsant Activity with the Selective Antagonist LY3130481 (CERC-611)
CNS & Neurological Disorders - Drug Targets Melatonin, its Metabolites and its Synthetic Analogs as Multi-Faceted Compounds: Antioxidant, Prooxidant and Inhibitor of Bioactivation Reactions
Current Medicinal Chemistry