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Alzheimer's disease cannabinoids

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https://www.readbyqxmd.com/read/29764526/cannabinoid-signalling-in-embryonic-and-adult-neurogenesis-possible-implications-for-psychiatric-and-neurological-disorders
#1
Rúbia W de Oliveira, Cilene L Oliveira, Francisco S Guimarães, Alline C Campos
Cannabinoid signalling modulates several aspects of brain function, including the generation and survival of neurons during embryonic and adult periods. The present review intended to summarise evidence supporting a role for the endocannabinoid system on the control of neurogenesis and neurogenesis-dependent functions. Studies reporting participation of cannabinoids on the regulation of any step of neurogenesis and the effects of cannabinoid compounds on animal models possessing neurogenesis-dependent features were selected from Medline...
May 16, 2018: Acta Neuropsychiatrica
https://www.readbyqxmd.com/read/29736745/activation-of-the-cannabinoid-type-2-receptor-by-a-novel-indazole-derivative-normalizes-the-survival-pattern-of-lymphoblasts-from-patients-with-late-onset-alzheimer-s-disease
#2
Patricia Del Cerro, Carolina Alquézar, Fernando Bartolomé, Pedro González-Naranjo, Concepción Pérez, Eva Carro, Juan A Páez, Nuria E Campillo, Ángeles Martín-Requero
BACKGROUND: Alzheimer's disease is a multifactorial disorder for which there is no disease-modifying treatment yet. CB2 receptors have emerged as a promising therapeutic target for Alzheimer's disease because they are expressed in neuronal and glial cells and their activation has no psychoactive effects. OBJECTIVE: The aim of this study was to investigate whether activation of the CB2 receptor would restore the aberrant enhanced proliferative activity characteristic of immortalized lymphocytes from patients with late-onset Alzheimer's disease...
May 7, 2018: CNS Drugs
https://www.readbyqxmd.com/read/29574668/cannabidiol-reverses-deficits-in-hippocampal-ltp-in-a-model-of-alzheimer-s-disease
#3
Blathnaid Hughes, Caroline E Herron
Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer's disease (AD). The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration. Hippocampal long-term potentiation (LTP) is an activity dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory...
March 24, 2018: Neurochemical Research
https://www.readbyqxmd.com/read/29501766/%C3%AE-amyrin-the-cannabinoid-receptors-agonist-abrogates-mice-brain-microglial-cells-inflammation-induced-by-lipopolysaccharide-interferon-%C3%AE-and-regulates-m%C3%AF-1-m%C3%AF-2-balances
#4
Vahid Reza Askari, Narges Fereydouni, Vafa Baradaran Rahimi, Nafiseh Askari, Amir Hossein Sahebkar, Pouria Rahmanian-Devin, Alireza Samzadeh-Kermani
BACKGROUND: Inflammation is a primary response to infection that can pathologically lead to various diseases including neurodegenerative diseases. The purpose of this study was to evaluate the effect of β-Amyrin, a naturally occurring pentacyclic triterpenoid compound, on inflammation induced by lipopolysaccharide (LPS) and interferone-γ (IFN-γ) in rat microglial cells. MATERIALS AND METHODS: Cytotoxicity of β-Amyrin (3-100) μM on microglial cells was evaluated using the MTT assay...
May 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29484980/innovative-therapeutic-potential-of-cannabinoid-receptors-as-targets-in-alzheimer-s-disease-and-less-well-known-diseases
#5
Juan A Paez, Nuria E Campillo
The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 being cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the first cannabinoid receptor (CB1) led to the isolation and characterisation of the first endocannabinoid, arachidonoylethanolamide (AEA), two years later and the subsequent identification of a family of lipid transmitters known as the fatty acid ester 2-arachidonoylglycerol (2-AG)...
February 25, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29454025/early-alteration-of-distribution-and-activity-of-hippocampal-type-1-cannabinoid-receptor-in-alzheimer-s-disease-like-mice-overexpressing-the-human-mutant-amyloid-precursor-protein
#6
Mauro Maccarrone, Antonio Totaro, Alessandro Leuti, Giacomo Giacovazzo, Lucia Scipioni, Dalila Mango, Roberto Coccurello, Robert Nisticò, Sergio Oddi
Besides its involvement in Alzheimer's disease (AD) as precursor of the neurotoxic amyloid peptides, the pathophysiological impact of brain accumulation of amyloid precursor protein (APP) is not yet well understood. Recent studies reported that APP interacts with other membrane proteins, including G protein coupled receptors, affecting their biological functions. Here, we focused on the study of the potential impact of human mutant APP on expression, distribution and activity of type-1 cannabinoid (CB1 ) receptor in the hippocampus of Tg2576 mice, an AD-like mice model...
April 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29400965/structure-activity-relationships-and-computational-investigations-into-the-development-of-potent-and-balanced-dual-acting-butyrylcholinesterase-inhibitors-and-human-cannabinoid-receptor-2-ligands-with-pro-cognitive-in-vivo-profiles
#7
Dominik Dolles, Matthias Hoffmann, Sandra Gunesch, Oliviero Marinelli, Jan Möller, Giorgio Santoni, Arnaud Chatonnet, Martin J Lohse, Hans-Joachim Wittmann, Andrea Strasser, Massimo Nabissi, Tangui Maurice, Michael Decker
The enzyme butyrylcholinesterase (BChE) and the human cannabinoid receptor 2 (hCB2 R) represent promising targets for pharmacotherapy in the later stages of Alzheimer's disease. We merged pharmacophores for both targets into small benzimidazole-based molecules, investigated SARs, and identified several dual-acting ligands with a balanced affinity/inhibitory activity and an excellent selectivity over both hCB1 R and hAChE. A homology model for the hCB2 R was developed based on the hCB1 R crystal structure and used for molecular dynamics studies to investigate binding modes...
February 22, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29390908/towards-a-better-understanding-of-the-cannabinoid-related-orphan-receptors-gpr3-gpr6-and-gpr12
#8
Paula Morales, Israa Isawi, Patricia H Reggio
GPR3, GPR6, and GPR12 are three orphan receptors that belong to the Class A family of G-protein-coupled receptors (GPCRs). These GPCRs share over 60% of sequence similarity among them. Because of their close phylogenetic relationship, GPR3, GPR6, and GPR12 share a high percentage of homology with other lipid receptors such as the lysophospholipid and the cannabinoid receptors. On the basis of sequence similarities at key structural motifs, these orphan receptors have been related to the cannabinoid family. However, further experimental data are required to confirm this association...
February 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29117869/frequency-of-use-of-the-international-classification-of-diseases-icd-10-diagnostic-categories-for-mental-and-behavioural-disorders-across-world-regions
#9
Y Faiad, B Khoury, S Daouk, M Maj, J Keeley, O Gureje, G Reed
AIMS: The study aimed to examine variations in the use of International Classification of Diseases, Tenth Edition (ICD-10) diagnostic categories for mental and behavioural disorders across countries, regions and income levels using data from the online World Psychiatric Association (WPA)-World Health Organization (WHO) Global Survey that examined the attitudes of psychiatrists towards the classification of mental disorders. METHODS: A survey was sent to 46 psychiatric societies which are members of WPA...
November 9, 2017: Epidemiology and Psychiatric Sciences
https://www.readbyqxmd.com/read/29073741/a-systematic-review-of-the-effectiveness-of-medical-cannabis-for-psychiatric-movement-and-neurodegenerative-disorders
#10
REVIEW
Keane Lim, Yuen Mei See, Jimmy Lee
The discovery of endocannabinoid's role within the central nervous system and its potential therapeutic benefits have brought forth rising interest in the use of cannabis for medical purposes. The present review aimed to synthesize and evaluate the available evidences on the efficacy of cannabis and its derivatives for psychiatric, neurodegenerative and movement disorders. A systematic search of randomized controlled trials of cannabis and its derivatives were conducted via databases (PubMed, Embase and the Cochrane Central Register of Controlled Trials)...
November 30, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29065845/identification-of-electrophysiological-changes-in-alzheimer-s-disease-a-microarray-based-transcriptomics-and-molecular-pathway-analysis-study
#11
Zeenat Mirza, Nisreen Rajeh
BACKGROUND & OBJECTIVE: Involvement of amyloid beta and tau proteins in pathogenesis of Alzheimer's disease (AD) has been studied extensively. However, electrophysiological activity, and cellular processes like membrane transport are mostly unstudied. Electrophysiological processes provide a bridge between brain activity and cognition, and show promise as translatable biomarkers in preclinical and clinical applications. Biochemical imbalance leads to change in glutamate-based neurotransmission, antioxidant capacity, and in membrane polarization-repolarization events, eventually, resulting in AD...
2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28968497/from-structure-activity-relationships-on-thiazole-derivatives-to-the-in-vivo-evaluation-of-a-new-radiotracer-for-cannabinoid-subtype-2-pet-imaging
#12
Fabien Caillé, Fanny Cacheux, Marie-Anne Peyronneau, Benoît Jego, Emilie Jaumain, Géraldine Pottier, Christoph Ullmer, Uwe Grether, Alexandra Winkeler, Frédéric Dollé, Annelaure Damont, Bertrand Kuhnast
Upregulation of the cannabinoid type 2 receptors (CB2R) unveils inflammation processes of pathological disorders, such as cancer, pain, or neurodegenerative diseases. Among others, CB2R agonist A-836339 has been labeled with carbon-11 for PET imaging of the CB2R and displayed promising results in a mouse model of Alzheimer's disease. The aim of the present work was to develop fluorinated analogs of A-836339 for labeling with fluorine-18 to design a new PET tracer for CB2R imaging. Seven fluorinated analogs of A-836339 were synthesized in two to three steps and their binding affinities and selectivities for both the human and the mouse CB2R were measured as well as their early ADME profiles...
November 6, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28844762/2-arachidonoylglycerol-metabolism-is-differently-modulated-by-oligomeric-and-fibrillar-conformations-of-amyloid-beta-in-synaptic-terminals
#13
Ana C Pascual, Virginia L Gaveglio, Norma M Giusto, Susana J Pasquaré
Alzheimer's disease (AD) is the most prevalent disorder of senile dementia mainly characterized by amyloid-beta peptide (Aβ) deposits in the brain. Cannabinoids are relevant to AD as they exert several beneficial effects in many models of this disease. Still, whether the endocannabinoid system is either up- or down-regulated in AD has not yet been fully elucidated. Thus, the aim of the present paper was to analyze endocannabinoid 2-arachidonoylglycerol (2-AG) metabolism in cerebral cortex synaptosomes incubated with Aβ oligomers or fibrils...
August 24, 2017: Neuroscience
https://www.readbyqxmd.com/read/28843453/receptor-heteromer-mediated-regulation-of-endocannabinoid-signaling-in-activated-microglia-role-of-cb1-and-cb2-receptors-and-relevance-for-alzheimer-s-disease-and-levodopa-induced-dyskinesia
#14
Gemma Navarro, Dasiel Borroto-Escuela, Edgar Angelats, Íñigo Etayo, Irene Reyes-Resina, Marta Pulido-Salgado, Ana I Rodríguez-Pérez, Enric I Canela, Josep Saura, José Luis Lanciego, José Luis Labandeira-García, Carlos A Saura, Kjell Fuxe, Rafael Franco
Endocannabinoids are important regulators of neurotransmission and, acting on activated microglia, they are postulated as neuroprotective agents. Endocannabinoid action is mediated by CB1 and CB2 receptors, which may form heteromeric complexes (CB1-CB2Hets) with unknown function in microglia. We aimed at establishing the expression and signaling properties of cannabinoid receptors in resting and LPS/IFN-γ-activated microglia. In activated microglia mRNA transcripts increased (2 fold for CB1 and circa 20 fold for CB2), whereas receptor levels were similar for CB1 and markedly upregulated for CB2; CB1-CB2Hets were also upregulated...
January 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28750813/methods-for-the-development-of-in-silico-gpcr-models
#15
Paula Morales, Dow P Hurst, Patricia H Reggio
The Reggio group has constructed computer models of the inactive and G-protein-activated states of the cannabinoid CB1 and CB2 receptors, as well as, several orphan receptors that recognize a subset of cannabinoid compounds, including GPR55 and GPR18. These models have been used to design ligands, mutations, and covalent labeling studies. The resultant second-generation models have been used to design ligands with improved affinity, efficacy, and subtype selectivity. Herein, we provide a guide for the development of GPCR models using the most recent orphan receptor studied in our lab, GPR3...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28733897/alleviation-of-neuropathology-by-inhibition-of-monoacylglycerol-lipase-in-app-transgenic-mice-lacking-cb2-receptors
#16
Jian Zhang, Chu Chen
Inhibition of monoacylglycerol lipase (MAGL), the primary enzyme that hydrolyzes the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain, produces profound anti-inflammatory and neuroprotective effects and improves synaptic and cognitive functions in animal models of Alzheimer's disease (AD). However, the molecular mechanisms underlying the beneficial effects produced by inhibition of 2-AG metabolism are still not clear. The cannabinoid receptor type 2 (CB2R) has been thought to be a therapeutic target for AD...
July 21, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28717968/deletion-of-type-2-cannabinoid-receptor-induces-alzheimer-s-disease-like-tau-pathology-and-memory-impairment-through-ampk-gsk3%C3%AE-pathway
#17
Lin Wang, Bing-Jin Liu, Yun Cao, Wei-Qi Xu, Dong-Sheng Sun, Meng-Zhu Li, Fang-Xiao Shi, Man Li, Qing Tian, Jian-Zhi Wang, Xin-Wen Zhou
Although several studies have shown that type-2 cannabinoid receptor (CB2R) is involved in Alzheimer's disease (AD) pathology, the effects of CB2R on AD-like tau abnormal phosphorylation and its underlying mechanism remain unclear. Herein, we employed the CB2R(-/-) mice as the animal model to explore roles of CB2R in regulating tau phosphorylation and brain function. We found that CB2R(-/-) mice display AD-like tau hyperphosphorylation, hippocampus-dependent memory impairment, increase of GSK3β activity, decrease of AMPK and Sirt1 activity and mitochondria dysfunction...
July 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28686542/polyunsaturated-fatty-acids-and-endocannabinoids-in-health-and-disease
#18
Hércules Rezende Freitas, Alinny Rosendo Isaac, Renato Malcher-Lopes, Bruno Lourenço Diaz, Isis Hara Trevenzoli, Ricardo Augusto De Melo Reis
Polyunsaturated fatty acids (PUFAs) are lipid derivatives of omega-3 (docosahexaenoic acid, DHA, and eicosapentaenoic acid, EPA) or of omega-6 (arachidonic acid, ARA) synthesized from membrane phospholipids and used as a precursor for endocannabinoids (ECs). They mediate significant effects in the fine-tune adjustment of body homeostasis. Phyto- and synthetic cannabinoids also rule the daily life of billions worldwide, as they are involved in obesity, depression and drug addiction. Consequently, there is growing interest to reveal novel active compounds in this field...
July 7, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28608697/perspectives-of-cannabinoid-type-2-receptor-cb2r-ligands-in-neurodegenerative-disorders-structure-affinity-relationship-safir-and-structure-activity-relationship-sar-studies
#19
Francesco Spinelli, Elena Capparelli, Carmen Abate, Nicola A Colabufo, Marialessandra Contino
Up-regulation of CB2R on activated microglial cells, the first step in neurodegeneration, has been widely demonstrated, and this finding makes the receptor a promising target in the early diagnosis and treatment of several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and multiple sclerosis (MS). The development of CB2R PET ligands could help demonstrate the neurodegenerative pathogenesis, thus providing useful tools for characterizing the role of neuroinflammation in the progression of these disorders...
December 28, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28571738/gpr3-and-gpr6-novel-molecular-targets-for-cannabidiol
#20
Alyssa S Laun, Zhao-Hui Song
GPR3 and GPR6 are members of a family of constitutively active, Gs protein-coupled receptors. Previously, it has been reported that GPR3 is involved in Alzheimer's disease whereas GPR6 plays potential roles in Parkinson's disease. GPR3 and GPR6 are considered orphan receptors because there are no confirmed endogenous agonists for them. However, GPR3 and GPR6 are phylogenetically related to the cannabinoid receptors. In this study, the activities of endocannabinoids and phytocannabinoids were tested on GPR3 and GPR6 using a β-arrestin2 recruitment assay...
August 12, 2017: Biochemical and Biophysical Research Communications
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