“Endocannabinoids (ECs) are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system (CNS). Activation of cannabinoid type 2 receptors (CB2) is known to diminish the release of pro-inflammatory factors and enhance the secretion of anti-inflammatory cytokines. Furthermore, the endocannabinoid 2-arachidonoyl glycerol (2-AG) has been proved to induce the migration of eosinophils in a CB2 receptor-dependent manner in peripheral blood and activate neutrophils independent of CB activation in humans. The present study revealed an upregulated endocannabinoid system in dogs with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29408878 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0187197]]>
Tag Archives: neuroprotection
Novel insights into mitochondrial molecular targets of iron-induced neurodegeneration: reversal by cannabidiol.
“Evidence has demonstrated iron accumulation in specific brain regions of patients suffering from neurodegenerative disorders, and this metal has been recognized as a contributing factor for neurodegeneration.
Using an experimental model of brain iron accumulation, we have shown that iron induces severe memory deficits that are accompanied by oxidative stress, increased apoptotic markers, and decreased synaptophysin in the hippocampus of rats.
The present study aims to characterize iron loading effects as well as to determine the molecular targets of cannabidiol (CBD), the main non-psychomimetic compound of Cannabis sativa, on mitochondria.
Rats received iron in the neonatal period and CBD for 14 days in adulthood. Iron induced mitochondrial DNA (mtDNA) deletions, decreased epigenetic modulation of mtDNA, mitochondrial ferritin levels, and succinate dehydrogenase activity.
CBD rescued mitochondrial ferritin and epigenetic modulation of mtDNA, and restored succinate dehydrogenase activity in iron-treated rats.
These findings provide new insights into molecular targets of iron neurotoxicity and give support for the use of CBD as a disease modifying agent in the treatment of neurodegenerative diseases.”
https://www.ncbi.nlm.nih.gov/pubmed/29374603
Analysis of endocannabinoid receptors and enzymes in the post-mortem motor cortex and spinal cord of amyotrophic lateral sclerosis patients.
“We have investigated the endocannabinoid system in the motor cortex of motor neuron disease (MND) patients.
CONCLUSION:
We have confirmed that CB2 receptors are elevated in the motor cortex of MND patients associated with the reactive gliosis. This phenomenon is previous to neuronal losses. We also found CB2 receptors in cortical and spinal motor neurons. These observations support that targeting this receptor may serve for developing neuroprotective therapies in MNDs.” https://www.ncbi.nlm.nih.gov/pubmed/29334787 http://www.tandfonline.com/doi/abs/10.1080/21678421.2018.1425454?journalCode=iafd20]]>Benefits of VCE-003.2, a cannabigerol quinone derivative, against inflammation-driven neuronal deterioration in experimental Parkinson's disease: possible involvement of different binding sites at the PPARγ receptor.
“Neuroprotection with cannabinoids in Parkinson’s disease (PD) has been afforded predominantly with antioxidant or anti-inflammatory cannabinoids. In the present study, we investigated the anti-inflammatory and neuroprotective properties of VCE-003.2, a quinone derivative of the non-psychotrophic phytocannabinoid cannabigerol (CBG), which may derive its activity at the peroxisome proliferator-activated receptor-γ (PPARγ). The compound is also an antioxidant. We have demonstrated that VCE-003.2 is neuroprotective against inflammation-driven neuronal damage in an in vivo model of PD and in in vitro cellular models of neuroinflammation. Such effects might involve PPARγ receptors, although in silico and in vitro experiments strongly suggest that VCE-003.2 targets PPARγ by acting through two binding sites at the LBP, one that is sensitive to T0070907 (canonical binding site) and other that is not affected by this PPARγ antagonist (alternative binding site).” https://www.ncbi.nlm.nih.gov/pubmed/29338785 https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1060-5]]>
WWL70 protects against chronic constriction injury-induced neuropathic pain in mice by cannabinoid receptor-independent mechanisms.
“Targeting the endocannabinoid system has emerged as an effective strategy for the treatment of inflammatory and neurological diseases.
Unlike the inhibition of the principal 2-arachidonyl glycerol (2-AG) hydrolytic enzyme monoacylglycerol lipase (MAGL), which leads to 2-AG overload and cannabinoid receptor desensitization, selective inhibition of the minor 2-AG hydrolytic enzyme alpha, beta-hydrolase domain 6 (ABHD6) can provide therapeutic benefits without producing cannabimimetic side effects. We have shown that inhibition of ABHD6 significantly reduces neuroinflammation and exerts neuroprotection in animal models of traumatic brain injury and multiple sclerosis. However, the role of ABHD6 inhibition on neuropathic pain has not been explored.
