Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer’s Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline

Altamura, Claudia; Ventriglia, Mariacarla; Martini, Maria Giulia; Montesano, Domenico; Errante, Yuri; Piscitelli, Fabiana; Scrascia, Federica; Quattrocchi, Carlo Cosimo; Palazzo, Paola; Seccia, Serenella; Vernieri, Fabrizio; Marzo, Vincenzo Di

doi:10.3233/jad-142349

Cited by 50 publications

(33 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The analysis of blood plasma revealed no changes in any of the endocannabinoids considered, and their levels showed no correlation with cognitive performance in healthy individuals at risk of AD [32]. Other authors, however, have found a significant increase in 2-AG and the AEA analog N-palmitoyl-ethanolamide levels in the blood plasma of patients with AD [33], and this could reflect a putative protective mechanism in the development of the disease. Interestingly, another report showed that an increase in FAAH mRNA and protein in peripheral blood mononuclear cells of patients with AD was linked to a decrease in the methylation state of the FAAH gene promoter region [34], thus suggesting a facilitation in gene expression.…”

Section: The Endocannabinoid System In Alzheimer's Diseasementioning

confidence: 81%

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Aymerich

Aso

Abellanas

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

The endocannabinoid system (ECS) exerts a modulatory effect of important functions such as neurotransmission, glial activation, oxidative stress, or protein homeostasis. Dysregulation of these cellular processes is a common neuropathological hallmark in aging and in neurodegenerative diseases of the central nervous system (CNS). The broad spectrum of actions of cannabinoids allows targeting different aspects of these multifactorial diseases. In this review, we examine the therapeutic potential of the ECS for the treatment of chronic neurodegenerative diseases of the CNS focusing on Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. First, we describe the localization of the molecular components of the ECS and how they are altered under neurodegenerative conditions, either contributing to or protecting cells from degeneration. Second, we address recent advances in the modulation of the ECS using experimental models through different strategies including the direct targeting of cannabinoid receptors with agonists or antagonists, increasing the endocannabinoid tone by the inhibition of endocannabinoid hydrolysis, and activation of cannabinoid receptor-independent effects. Preclinical evidence indicates that cannabinoid pharmacology is complex but supports the therapeutic potential of targeting the ECS. Third, we review the clinical evidence and discuss the future perspectives on how to bridge human and animal studies to develop cannabinoid-based therapies for each neurodegenerative disorder. Finally, we summarize the most relevant opportunities of cannabinoid pharmacology related to each disease and the multiple unexplored pathways in cannabinoid pharmacology that could be useful for the treatment of neurodegenerative diseases.

show abstract

Section: The Endocannabinoid System In Alzheimer's Diseasementioning

confidence: 81%

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Aymerich

Aso

Abellanas

et al. 2018

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…As noted above, circulating 2-AG concentrations are significantly, negatively correlated with memory in individuals with osteoporosis (La Porta et al, 2014). On the other hand, plasma 2-AG concentrations are significantly higher in individuals diagnosed with Alzheimer's Disease (AD) compared to matched controls and are positively correlated with memory and attention in those with AD (Altamura et al, 2015). Yet another study found no differences in circulating endocannabinoid concentrations between patients with AD and controls (Koppel et al, 2009).…”

Section: Endocannabinoids and Cognitionmentioning

confidence: 95%

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Hillard

2017

Neuropsychopharmacol.

322

241

View full text Add to dashboard Cite

The goal of this review is to summarize studies in which concentrations of circulating endocannabinoids in humans have been examined in relationship to physiological measurements and pathological status. The roles of endocannabinoids in the regulation of energy intake and storage have been well studied and the data obtained consistently support the hypothesis that endocannabinoid signaling is associated with increased consumption and storage of energy. Physical exercise mobilizes endocannabinoids, which could contribute to refilling of energy stores and also to the analgesic and mood-elevating effects of exercise. Circulating concentrations of 2-arachidonoylglycerol are very significantly circadian and dysregulated when sleep is disrupted. Other conditions under which circulating endocannabinoids are altered include inflammation and pain. A second important role for endocannabinoid signaling is to restore homeostasis following stress. Circulating endocannabinoids are stress-responsive and there is evidence that their concentrations are altered in disorders associated with excessive stress, including post-traumatic stress disorder. Although determination of circulating endocannabinoids can provide important information about the state of endocannabinoid signaling and thus allow for hypotheses to be defined and tested, the large number of physiological factors that contribute to their circulating concentrations makes it difficult to use them in isolation as a biomarker for a specific disorder.

show abstract

“…Studies revealed that basal nuclei areas and greater oval centers are rich in a large number of neurons and fibers closely associated with cognitive functions such as learning and memory. [14][15][16][17] By means of multi-layer spiral CT examination, our study found that the CBF and CBV in bilateral basal ganglia, frontal lobes, greater oval center, brain stem, and left and right regions of occipital lobes of the patients in CCCI group were significantly lower than those seen in the depression group, which leads to decrease in the cognitive functions of the CCCI patients.…”

Section: Discussionmentioning

confidence: 61%

Analyzing the neuropsychological characteristics and changes in serum markers of patients with chronic cerebral circulation insufficiency

Tang

Zhen

et al. 2018

Rev. Assoc. Med. Bras.

View full text Add to dashboard Cite

show abstract

Elevation of Plasma 2-Arachidonoylglycerol Levels in Alzheimer’s Disease Patients as a Potential Protective Mechanism against Neurodegenerative Decline

Cited by 50 publications

References 61 publications

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Cannabinoid pharmacology/therapeutics in chronic degenerative disorders affecting the central nervous system

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

Analyzing the neuropsychological characteristics and changes in serum markers of patients with chronic cerebral circulation insufficiency

Contact Info

Product

Resources

About