Category

Alzheimer’s Disease

Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells.

By | Alzheimer's Disease

Authors:

Rosaliana Libro, Francesca Diomede, Domenico Scionti, Adriano Piattelli, Gianpaolo Grassi, Federica Pollastro, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani


Published in International Journal of Molecular Sciences

23 December 2016

 

Abstract

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of several neurodegenerative disorders, including Alzheimer’s disease (AD). The main neuropathological hallmarks of AD are senile plaques, composed of amyloid beta (Aβ), and neurofibrillary tangles, formed by hyperphosphorylated tau. However, current therapies for AD have shown limited efficacy. In this study, we evaluated whether pre-treatment with cannabidiol (CBD), at 5 μM concentration, modulated the transcriptional profile of MSCs derived from gingiva (GMSCs) in order to improve their therapeutic potential, by performing a transcriptomic analysis by the next-generation sequencing (NGS) platform. By comparing the expression profiles between GMSCs treated with CBD (CBD-GMSCs) and control GMSCs (CTR-GMSCs), we found that CBD led to the downregulation of genes linked to AD, including genes coding for the kinases responsible of tau phosphorylation and for the secretases involved in Aβ generation. In parallel, immunocytochemistry analysis has shown that CBD inhibited the expression of GSK3β, a central player in AD pathogenesis, by promoting PI3K/Akt signalling. In order to understand through which receptor CBD exerted these effects, we have performed pre-treatments with receptor antagonists for the cannabinoid receptors (SR141716A and AM630) or for the vanilloid receptor 1 (TRPVI). Here, we have proved that TRPV1 was able to mediate the modulatory effect of CBD on the PI3K/Akt/GSK3β axis. In conclusion, we have found that pre-treatment with CBD prevented the expression of proteins potentially involved in tau phosphorylation and Aβ production in GMSCs. Therefore, we suggested that GMSCs preconditioned with CBD possess a molecular profile that might be more beneficial for the treatment of AD.

 

DOI: 10.3390/ijms18010026

Full Text

Citation:

Libro R, Diomede F, Scionti D, et al. Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells. International Journal of Molecular Sciences. 2016;18(1):26. doi:10.3390/ijms18010026.

Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

By | Alzheimer's Disease

Authors:

Ester Aso, Isidre Ferrer


Published in Frontiers in Pharmacology

5 March 2014

 

Abstract

The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer. The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors, with their endogenous ligands and the enzymes related to the synthesis and degradation of these endocannabinoid compounds. Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models by reducing the harmful β-amyloid peptide action and tau phosphorylation, as well as by promoting the brain’s intrinsic repair mechanisms. Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress. The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.

 

DOI: 10.3389/fphar.2014.00037

Full Text

Citation:

Aso E, Ferrer I. Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic. Frontiers in Pharmacology. 2014;5(37). doi:10.3389/fphar.2014.00037.

A molecular link between the active component of marijuana and Alzheimer’s disease pathology.

By | Alzheimer's Disease

Authors:

Lisa M. Eubanks, Claude J. Rogers, George F. Koob, Arthur J. Olson, Tobin J. Dickerson, Kim D. Janda


Published in Molecular Pharmaceutics

2006

 

Abstract

Alzheimer’s disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer’s disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer’s disease. Here, we demonstrate that the active component of marijuana, Delta9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of Alzheimer’s disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Abeta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.

 

DOI: 10.1021/mp060066m

Author Manuscript

Citation:

Eubanks LM, Rogers CJ, Beuscher, et al. A Molecular Link between the Active Component of Marijuana and Alzheimers Disease Pathology. Molecular Pharmaceutics. 2006;3(6):773-777. doi:10.1021/mp060066m.

Russo’s Grand Unified Theory

By | Alzheimer's Disease, Brain Trauma, Cancer, Conditions, Epilepsy, News, Parkinson's, Research, Research Articles

Ethan Russo forwards his paper, Grand Unified Theory (GUT): The Endcannabinoid System, Cannabis and the Microbiome just published in Frontiers of Integrative Neuroscience. Russo notes:

“This article addresses five critical areas of clinical neurology practice wherein conventional medicine has fallen short: epilepsy, brain tumors, Parkinson disease, Alzheimer disease, traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE), and how cannabis-based treatment and nutritional approaches with prebiotics and probiotics may provide more effective treatment.”

The paper, which will be the basis of Russo’s talk at the CannMed conference in LA October 23, begins with this overview:

Neurological therapeutics have been hampered by its inability to advance beyond symptomatic treatment of neurodegenerative disorders into the realm of actual palliation, arrest or reversal of the attendant pathological processes. While cannabis-based medicines have demonstrated safety, efficacy and consistency sufficient for regulatory approval in spasticity in multiple sclerosis (MS), and in Dravet and Lennox-Gastaut Syndromes (LGS), many therapeutic challenges remain. This review will examine the intriguing promise that recent discoveries regarding cannabis-based medicines offer to neurological therapeutics by incorporating the neutral phytocannabinoids tetrahydrocannabinol (THC), cannabidiol (CBD), their acidic precursors, tetrahydrocannabinolic acid (THCA) and cannabidiolic acid (CBDA), and cannabis terpenoids in the putative treatment of five syndromes, currently labeled recalcitrant to therapeutic success, and wherein improved pharmacological intervention is required: intractable epilepsy, brain tumors, Parkinson disease (PD), Alzheimer disease (AD) and traumatic brain injury (TBI)/chronic traumatic encephalopathy (CTE). Current basic science and clinical investigations support the safety and efficacy of such interventions in treatment of these currently intractable conditions, that in some cases share pathological processes, and the plausibility of interventions that harness endocannabinoid mechanisms, whether mediated via direct activity on CB1 and CB2(tetrahydrocannabinol, THC, caryophyllene), peroxisome proliferator-activated receptor-gamma (PPARγ; THCA), 5-HT1A (CBD, CBDA) or even nutritional approaches utilizing prebiotics and probiotics. The inherent polypharmaceutical properties of cannabis botanicals offer distinct advantages over the current single-target pharmaceutical model and portend to revolutionize neurological treatment into a new reality of effective interventional and even preventative treatment. Read More

A Molecular Link Between the Active Component of Cannabis and Alzheimer’s Disease Pathology

By | Alzheimer's Disease, Brain Health, Research Articles

Medical Cannabis and Alzheimer's Disease

As reported in a 2006 issue of Molecular Pharmacology: “Compared to currently approved drugs prescribed for the treatment of Alzheimer’s disease, THC is a considerably superior inhibitor of Aβ aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.” Read More

Cannabidiol: From an Inactive Cannabinoid to a Drug with Wide Spectrum of Action

By | Alzheimer's Disease, Arthritis, Cancer, CBD, Diabetes, Nausea, Research Articles

CBD Health Benefits for Parkinson's, Diabetes, and More

The years 2003 – 2008 showed a remarkable increase in publications on cannabidiol mainly stimulated by the discovery of its anti-inflammatory, anti-oxidative and neuroprotective effects. These studies have suggested a wide range of possible therapeutic effects of cannabidiol on several conditions, including Parkinson’s disease, Alzheimer’s disease, cerebral ischemia, diabetes, rheumatoid arthritis, other inflammatory diseases, nausea and cancer. Read More