Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation
Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB<sub>1/2</sub>, mediate multiple mechanisms of intercellular communication within the body. Endocannabin...
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doaj-321ec4371ef64d14aa2039eacaa2292d2021-06-01T00:41:58ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01225431543110.3390/ijms22115431Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under NeuroinflammationLudmila A. Kasatkina0Sonja Rittchen1Eva M. Sturm2Otto Loewi Research Center, Division of Pharmacology, Medical University of Graz, 8010 Graz, AustriaOtto Loewi Research Center, Division of Pharmacology, Medical University of Graz, 8010 Graz, AustriaOtto Loewi Research Center, Division of Pharmacology, Medical University of Graz, 8010 Graz, AustriaEndocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB<sub>1/2</sub>, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB<sub>1/2</sub>, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy.https://www.mdpi.com/1422-0067/22/11/5431endocannabinoidsN-acylethanolaminesneuroinflammationglutamate-mediated excitotoxicityneurodegenerative diseasessynaptic plasticity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ludmila A. Kasatkina Sonja Rittchen Eva M. Sturm |
spellingShingle |
Ludmila A. Kasatkina Sonja Rittchen Eva M. Sturm Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation International Journal of Molecular Sciences endocannabinoids N-acylethanolamines neuroinflammation glutamate-mediated excitotoxicity neurodegenerative diseases synaptic plasticity |
author_facet |
Ludmila A. Kasatkina Sonja Rittchen Eva M. Sturm |
author_sort |
Ludmila A. Kasatkina |
title |
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation |
title_short |
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation |
title_full |
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation |
title_fullStr |
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation |
title_full_unstemmed |
Neuroprotective and Immunomodulatory Action of the Endocannabinoid System under Neuroinflammation |
title_sort |
neuroprotective and immunomodulatory action of the endocannabinoid system under neuroinflammation |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-05-01 |
description |
Endocannabinoids (eCBs) are lipid-based retrograde messengers with a relatively short half-life that are produced endogenously and, upon binding to the primary cannabinoid receptors CB<sub>1/2</sub>, mediate multiple mechanisms of intercellular communication within the body. Endocannabinoid signaling is implicated in brain development, memory formation, learning, mood, anxiety, depression, feeding behavior, analgesia, and drug addiction. It is now recognized that the endocannabinoid system mediates not only neuronal communications but also governs the crosstalk between neurons, glia, and immune cells, and thus represents an important player within the neuroimmune interface. Generation of primary endocannabinoids is accompanied by the production of their congeners, the N-acylethanolamines (NAEs), which together with N-acylneurotransmitters, lipoamino acids and primary fatty acid amides comprise expanded endocannabinoid/endovanilloid signaling systems. Most of these compounds do not bind CB<sub>1/2</sub>, but signal via several other pathways involving the transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor (PPAR)-α and non-cannabinoid G-protein coupled receptors (GPRs) to mediate anti-inflammatory, immunomodulatory and neuroprotective activities. In vivo generation of the cannabinoid compounds is triggered by physiological and pathological stimuli and, specifically in the brain, mediates fine regulation of synaptic strength, neuroprotection, and resolution of neuroinflammation. Here, we review the role of the endocannabinoid system in intrinsic neuroprotective mechanisms and its therapeutic potential for the treatment of neuroinflammation and associated synaptopathy. |
topic |
endocannabinoids N-acylethanolamines neuroinflammation glutamate-mediated excitotoxicity neurodegenerative diseases synaptic plasticity |
url |
https://www.mdpi.com/1422-0067/22/11/5431 |
work_keys_str_mv |
AT ludmilaakasatkina neuroprotectiveandimmunomodulatoryactionoftheendocannabinoidsystemunderneuroinflammation AT sonjarittchen neuroprotectiveandimmunomodulatoryactionoftheendocannabinoidsystemunderneuroinflammation AT evamsturm neuroprotectiveandimmunomodulatoryactionoftheendocannabinoidsystemunderneuroinflammation |
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