Cannabinoids and Neurodegenerative Disorders

2017 ◽  
Author(s):  
Linda A. Parker
Keyword(s):  
Glutamate Release ◽  
Endocannabinoid System ◽  
Preclinical Research ◽  
Neuroprotective Effects ◽  
Amyotropic Lateral Sclerosis ◽  
System P ◽  
Clinical Trial Evidence ◽  
Anti Oxidant ◽  
Neuroprotective Function ◽  
Trial Evidence

Cannabinoids play a neuroprotective function in the brain by reducing the release of excitatory glutamate release and by their anti-oxidant and anti-inflammatory effects. THC acts on both CB1 and CB2 receptors, both of which have been shown to be important in the neuroprotective effects of the endocannabinoid system, such as reducing the damage produced by stroke. The best human clinical trial evidence for the effectiveness of cannabis as a medicine is in the treatment of painful spasticity in Multiple Sclerosis (MS) patients. Preclinical research suggests that the endocannabinoid system is also involved in symptomatology of Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and Amyotropic Lateral Sclerosis, suggesting that treatments with activate this system, may be useful treatments for a range of neurogenerative disorders of the nervous system.

In silico and In vivo Evaluation of Oxidative Stress Inhibitors Against Parkinson`s Disease using the C. elegans Model

2020 ◽  
Vol 23 (8) ◽  
pp. 814-826
Author(s):  
Pradeep Hanumanthappa ◽  
Arpitha Ashok ◽  
Inderjit Prakash ◽  
Carmel I. Priya ◽  
Julie Zinzala ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Neurodegenerative Disorder ◽  
In Vivo Evaluation ◽  
Neuroprotective Effects ◽  
Ample Evidence ◽  
C Elegans ◽  
Rational Drug ◽  
Cullin 3 ◽  
Anti Oxidant

Background: Parkinson’s disease ranks second, after Alzheimer’s as the major neurodegenerative disorder, for which no cure or disease-modifying therapies exist. Ample evidence indicate that PD manifests as a result of impaired anti-oxidative machinery leading to neuronal death wherein Cullin-3 has ascended as a potential therapeutic target for diseases involving damaged anti-oxidative machinery. Objective: The design of target specific inhibitors for the Cullin-3 protein might be a promising strategy to increase the Nrf2 levels and to decrease the possibility of “off-target” toxic properties. Methods: In the present study, an integrated computational and wet lab approach was adopted to identify small molecule inhibitors for Cullin-3. The rational drug designing process comprised homology modeling and derivation of the pharmacophore for Cullin-3, virtual screening of Zinc natural compound database, molecular docking and Molecular dynamics based screening of ligand molecules. In vivo validations of an identified lead compound were conducted in the PD model of C. elegans. Results and Discussion: Our strategy yielded a potential inhibitor; (Glide score = -12.31), which was evaluated for its neuroprotective efficacy in the PD model of C. elegans. The inhibitor was able to efficiently defend against neuronal death in PD model of C. elegans and the neuroprotective effects were attributed to its anti-oxidant activities, supported by the increase in superoxide dismutase, catalase and the diminution of acetylcholinesterase and reactive oxygen species levels. In addition, the Cullin-3 inhibitor significantly restored the behavioral deficits in the transgenic C. elegans. Conclusion: Taken together, these findings highlight the potential utility of Cullin-3 inhibition to block the persistent neuronal death in PD. Further studies focusing on Cullin-3 and its mechanism of action would be interesting.

scholarly journals Updated Review and Meta-Analysis of Probiotics for the Treatment of Clinical Depression: Adjunctive vs. Stand-Alone Treatment

2021 ◽  
Vol 10 (4) ◽  
pp. 647
Author(s):  
Viktoriya L. Nikolova ◽  
Anthony J. Cleare ◽  
Allan H. Young ◽  
James M. Stone
Keyword(s):  
Meta Analysis ◽  
Clinical Depression ◽  
Controlled Clinical Trial ◽  
Reactive Protein ◽  
Treatment Type ◽  
Antidepressant Effects ◽  
Clinical Trial Evidence ◽  
Randomised Controlled ◽  
Trial Evidence ◽  
Insight Into

Recent years have seen a rapid increase in the use of gut microbiota-targeting interventions, such as probiotics, for the treatment of psychiatric disorders. The objective of this update review was to evaluate all randomised controlled clinical trial evidence on the efficacy of probiotics for clinical depression. Cochrane guidelines for updated reviews were followed. By searching PubMed and Web of Science databases, we identified 546 new records since our previous review. A total of seven studies met selection criteria, capturing 404 people with depression. A random effects meta-analysis using treatment type (stand-alone vs. adjunctive) as subgroup was performed. The results demonstrated that probiotics are effective in reducing depressive symptoms when administered in addition to antidepressants (SMD = 0.83, 95%CI 0.49–1.17), however, they do not seem to offer significant benefits when used as stand-alone treatment (SMD = −0.02, 95%CI −0.34–0.30). Potential mechanisms of action may be via increases in brain-derived neurotrophic factor (BDNF) and decreases in C-reactive protein (CRP), although limited evidence is available at present. This review offers stronger evidence to support the clinical use of probiotics in depressed populations and provides an insight into the mode of administration more likely to yield antidepressant effects.

scholarly journals Sulfonylureas at the Glomerular Battlefield

2018 ◽  
Vol 14 (2) ◽  
pp. 15
Author(s):  
Sanjay Kalra ◽  
Deepak Khandelwal ◽  
Sarita Bajaj ◽  
Ashok Kumar Das
Keyword(s):  
Clinical Trial ◽  
Glucose Homeostasis ◽  
Diabetes Complications ◽  
Cardiovascular Health ◽  
Glucose Lowering ◽  
Meeting Point ◽  
Normal Glucose ◽  
Clinical Trial Evidence ◽  
Trial Evidence

The kidney is important in the context of diabetes not only because it is involved in normal glucose homeostasis, but also because it is one of the most important end organs to be involved in diabetes complications. Glomeruli are the meeting point of both microvascular, or renal; and macrovascular, or cardiovascular, health in diabetes. Sulfonylureas are effective glucose-lowering drugs. While a sulfonylurea-based glucose-lowering strategy is nephro-safe and nephro-protective, this aspect of sulfonylurea pharmaco-biology has not been highlighted earlier. In this editorial, we discuss current preclinical and clinical trial evidence regarding the performance of modern sulfonylureas at the glomerular battlefield.

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