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Alzheimer's disease cannabinoids

Rosario Gajardo-Gómez, Valeria C Labra, Carola J Maturana, Kenji F Shoji, Cristian A Santibañez, Juan C Sáez, Christian Giaume, Juan A Orellana
The mechanisms involved in Alzheimer's disease are not completely understood and how astrocytes and their gliotransmission contribute to this neurodegenerative disease remains to be fully elucidated. Previous studies have shown that amyloid-β peptide (Aβ) induces neuronal death by a mechanism that involves the excitotoxic release of ATP and glutamate associated to astroglial hemichannel opening. We have demonstrated that synthetic and endogenous cannabinoids (CBs) reduce the opening of astrocyte Cx43 hemichannels evoked by activated microglia or inflammatory mediators...
October 19, 2016: Glia
Thangavelu Soundara Rajan, Domenico Scionti, Francesca Diomede, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Lucio Cocco, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
Research in recent years has extensively investigated the therapeutic efficacy of mesenchymal stromal cells in regenerative medicine for many neurodegenerative diseases at preclinical and clinical stages. However, the success rate of stem cell therapy remains less at translational phase. Lack of relevant animal models that potentially simulate the molecular etiology of human pathological symptoms might be a reason behind such poor clinical outcomes associated with stem cell therapy. Apparently, self-renewal and differentiation ability of mesenchymal stem cells may help to study the early developmental signaling pathways connected with the diseases, such as Alzheimer's disease, Amyotrophic lateral sclerosis (ALS), etc...
October 7, 2016: Journal of Cellular Biochemistry
Jorge Navarro-Dorado, Nuria Villalba, Dolores Prieto, Begoña Brera, Ana M Martín-Moreno, Teresa Tejerina, María L de Ceballos
There is evidence of altered vascular function, including cerebrovascular, in Alzheimer's disease (AD) and transgenic models of the disease. Indeed vasoconstrictor responses are increased, while vasodilation is reduced in both conditions. β-Amyloid (Aβ) appears to be responsible, at least in part, of alterations in vascular function. Cannabinoids, neuroprotective and anti-inflammatory agents, induce vasodilation both in vivo and in vitro. We have demonstrated a beneficial effect of cannabinoids in models of AD by preventing glial activation...
2016: Frontiers in Neuroscience
Shalini Jayant, Bhupesh Sharma
Vascular dementia is the highly devastating neurodegenerative disorder after Alzheimer's disease (AD) and mainly found in aged people but the effectual therapeutic target is still not there. Chronic cerebral hypoperfusion (CCH) has been broadly found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive deteriorate on. This study has been framed to examine the role of a selective agonist of cannabinoid receptor type 2(CB2); 1-phenylisatin in CCH induced VaD...
September 2, 2016: Current Neurovascular Research
Ester Aso, Pol Andrés-Benito, Isidro Ferrer
Previous reports have demonstrated that the combination of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) botanical extracts, which are the components of an already approved cannabis-based medicine, reduce the Alzheimer-like phenotype of AβPP/PS1 transgenic mice when chronically administered during the early symptomatic stage. Here, we provide evidence that such natural cannabinoids are still effective in reducing memory impairment in AβPP/PS1 mice at advanced stages of the disease but are not effective in modifying the Aβ processing or in reducing the glial reactivity associated with aberrant Aβ deposition as occurs when administered at early stages of the disease...
October 4, 2016: Journal of Alzheimer's Disease: JAD
Samuel T Wilkinson, Rajiv Radhakrishnan, Deepak Cyril D'Souza
OBJECTIVE: Marijuana has been approved for a number of psychiatric conditions in many states in the US including posttraumatic stress disorder (PTSD), agitation in Alzheimer's disease, and Tourette's disorder. In this systematic review, we examine the strength of evidence for the efficacy of marijuana and other cannabinoids for these psychiatric indications. DATA SOURCES: The literature (MEDLINE) was searched for studies published between January 1980 and March 2015 using search terms related to marijuana and other cannabinoids and the specific diagnosis...
August 2016: Journal of Clinical Psychiatry
Rawaha Ahmad, Andrey Postnov, Guy Bormans, Jan Versijpt, Mathieu Vandenbulcke, Koen Van Laere
PURPOSE: The cannabinoid type 2 receptor (CB2R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB2R is primarily found on microglia. CB2R upregulation has been reported in animal models of Alzheimer's disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB2R tracer [(11)C]NE40 in healthy controls (HC) and in patients with Alzheimer's disease (AD) to investigate whether higher CB2R availability regionally colocalized to Aβ deposits is present in vivo...
November 2016: European Journal of Nuclear Medicine and Molecular Imaging
Tiziana Bisogno, Sergio Oddi, Alessandra Piccoli, Domenico Fazio, Mauro Maccarrone
Based on its wide expression in immune cells, type-2 cannabinoid (CB2) receptors were traditionally thought to act as "peripheral receptors" with an almost exclusively immunomodulatory function. However, their recent identification in mammalian brain areas, as well as in distinct neuronal cells, has opened the way to a re-consideration of CB2 signaling in the context of brain pathophysiology, synaptic plasticity and neuroprotection. To date, accumulated evidence from several independent preclinical studies has offered new perspectives on the possible involvement of CB2 signaling in brain and spinal cord traumatic injury, as well as in the most relevant neurodegenerative disorders like Alzheimer's disease, Parkinson's disease and Huntington's chorea...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Maurizio Bifulco, Chiara Laezza, Anna Maria Malfitano
BACKGROUND: Several studies support the evidence that the endocannabinoid system and cannabimimetic drugs might have therapeutic potential in numerous pathologies. These pathologies range from neurological disorders, atherosclerosis, stroke, cancer to obesity/metabolic syndrome and others. METHODS: In this paper we review the endocannabinoid system signaling and its alteration in neurodegenerative disorders like multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease and discuss the main findings about the use of cannabinoids in the therapy of these pathologies...
June 27, 2016: Recent Patents on CNS Drug Discovery
Ester Aso, Isidro Ferrer
The CB2 receptor is one of the components of the endogenous cannabinoid system, a complex network of signaling molecules and receptors involved in the homeostatic control of several physiological functions. Accumulated evidence suggests a role for CB2 receptors in Alzheimer's disease (AD) and indicates their potential as a therapeutic target against this neurodegenerative disease. Levels of CB2 receptors are significantly increased in post-mortem AD brains, mainly in microglia surrounding senile plaques, and their expression levels correlate with the amounts of Aβ42 and β-amyloid plaque deposition...
2016: Frontiers in Neuroscience
Iván Manuel, Laura Lombardero, Frank M LaFerla, Lydia Giménez-Llort, Rafael Rodríguez-Puertas
Neurochemical alterations in Alzheimer's disease (AD) include cholinergic neuronal loss in the nucleus basalis of Meynert (nbM) and a decrease in densities of the M2 muscarinic receptor subtype in areas related to learning and memory. Neuromodulators present in the cholinergic pathways, such as neuropeptides and neurolipids, control these cognitive processes and have become targets of research in order to understand and treat the pathophysiological and clinical stages of the disease. This is the case of the endocannabinoid and galaninergic systems, which have been found to be up-regulated in AD, and could therefore have a neuroprotective role...
August 4, 2016: Neuroscience
Celina S Liu, Myuri Ruthirakuhan, Sarah A Chau, Nathan Herrmann, André F Carvalho, Krista L Lanctôt
Agitation and aggression are common neuropsychiatric symptoms of Alzheimer's disease and are highly prevalent in people with dementia. When pharmacological intervention becomes necessary, current clinical practice guidelines recommend antipsychotics, cholinesterase inhibitors, and some antidepressants. However, those interventions have modest to low efficacy, and those with the highest demonstrated efficacy have significant safety concerns. As a result, current research is focusing on novel compounds that have different mechanisms of action and that may have a better balance of efficacy over safety...
2016: Current Alzheimer Research
Rosaliana Libro, Sabrina Giacoppo, Thangavelu Soundara Rajan, Placido Bramanti, Emanuela Mazzon
The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common. Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required...
2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Rimplejeet Kaur, Sneha R Ambwani, Surjit Singh
Cannabis sativa is also popularly known as marijuana. It has been cultivated and used by man for recreational and medicinal purposes since many centuries. Study of cannabinoids was at bay for very long time and its therapeutic value could not be adequately harnessed due to its legal status as proscribed drug in most of the countries. The research of drugs acting on endocannabinoid system has seen many ups and downs in the recent past. Presently, it is known that endocannabinoids has role in pathology of many disorders and they also serve "protective role" in many medical conditions...
2016: Current Clinical Pharmacology
Attila Köfalvi, Cristina Lemos, Ana M Martín-Moreno, Bárbara S Pinheiro, Luis García-García, Miguel A Pozo, Ângela Valério-Fernandes, Rui O Beleza, Paula Agostinho, Ricardo J Rodrigues, Susana J Pasquaré, Rodrigo A Cunha, María L de Ceballos
Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain. To that aim, we have undertaken 1) measurement of (3)H-deoxyglucose uptake in cultured cortical astrocytes and neurons and in acute hippocampal slices; 2) real-time visualization of fluorescently labeled deoxyglucose uptake in superfused hippocampal slices; and 3) in vivo PET imaging of cerebral (18)F-fluorodeoxyglucose uptake...
November 2016: Neuropharmacology
Ester Aso, Pol Andrés-Benito, Margarita Carmona, Rafael Maldonado, Isidre Ferrer
The endogenous cannabinoid system represents a promising therapeutic target to modify neurodegenerative pathways linked to Alzheimer's disease (AD). The aim of the present study was to evaluate the specific contribution of CB2 receptor to the progression of AD-like pathology and its role in the positive effect of a cannabis-based medicine (1:1 combination of Δ9-tetrahidrocannabinol and cannabidiol) previously demonstrated to be beneficial in the AβPP/PS1 transgenic model of the disease. A new mouse strain was generated by crossing AβPP/PS1 transgenic mice with CB2 knockout mice...
2016: Journal of Alzheimer's Disease: JAD
Ji Jia, Jie Peng, Zhaoju Li, Youping Wu, Qunlin Wu, Weifeng Tu, Mingchun Wu
BACKGROUND: Reducing β amyloid- (Aβ-) induced microglial activation is considered to be effective in treating Alzheimer's disease (AD). Nicotine attenuates Aβ-induced microglial activation; the mechanism, however, is still elusive. Microglia could be activated into classic activated state (M1 state) or alternative activated state (M2 state); the former is cytotoxic and the latter is neurotrophic. In this investigation, we hypothesized that nicotine attenuates Aβ-induced microglial activation by shifting microglial M1 to M2 state, and cannabinoid CB2 receptor and protein kinase C mediate the process...
2016: Mediators of Inflammation
Ryan C McCarthy, Dah-Yuu Lu, Ahmed Alkhateeb, Andrew M Gardeck, Chih-Hao Lee, Marianne Wessling-Resnick
BACKGROUND: Alzheimer's disease is associated with amyloid-beta (Aβ)-induced microglia activation. This pro-inflammatory response promotes neuronal damage, and therapies are sought to limit microglial activation. Screening efforts to develop new pharmacological inhibitors require a robust in vitro cell system. Current models lack significant responses to Aβ, and their use in examining age-related neurodegenerative diseases is questionable. For example, the commonly used BV-2 microglial line was derived from embryonic mononuclear cells and its activation by various stimuli is limited...
2016: Journal of Neuroinflammation
Orla Haugh, June Penman, Andrew J Irving, Veronica A Campbell
The classical endogenous cannabinoid (CB) system is composed of the endocannabinoid signalling molecules, 2-arachidonoyl glycerol (2-AG) and anandamide (AEA) and their G-protein coupled receptors (GPCR), CB1 and CB2 which together constitutes the endocannabinoid system (ECS). However, putative, novel lipid-sensing CB receptors have recently been identified, including the orphan GPR55 and GPR18 receptors that are regulated by cannabinoid-like molecules and interact with CB system. CB receptors and associated orphan GPCRs are expressed at high levels in the immune and/or central nervous systems (CNS) and regulate a number of neurophysiological processes, including key events involved in neuroinflammation...
January 11, 2016: Current Drug Targets
Bieneke Janssen, Danielle J Vugts, Uta Funke, Ger T Molenaar, Perry S Kruijer, Bart N M van Berckel, Adriaan A Lammertsma, Albert D Windhorst
Neuroinflammation is thought to play a pivotal role in many diseases affecting the brain, including Alzheimer's disease, multiple sclerosis and stroke. Neuroinflammation is characterised predominantly by microglial activation, which can be visualised using positron emission tomography (PET). Traditionally, translocator protein 18kDa (TSPO) is the target for imaging of neuroinflammation using PET. In this review, recent preclinical and clinical research using PET in Alzheimer's disease, multiple sclerosis and stroke is summarised...
March 2016: Biochimica et Biophysica Acta
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