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https://www.readbyqxmd.com/read/28077796/tumor-cell-migration-is-inhibited-by-a-novel-therapeutic-strategy-antagonizing-the-alpha-7-receptor
#1
Chris Pepper, Henry Tu, Paul Morrill, Sara Garcia-Rates, Chris Fegan, Susan Greenfield
A 14mer peptide (T14) derived from the C-terminus of acetylcholinesterase (AChE) selectively activates metastatic breast cancer cells via the alpha-7 nicotinic receptor (α7 nAChR). This naturally occurring peptide is also present in brain, is elevated in Alzheimer's disease, and is antagonised by a cyclized variant (NBP-14). Here we investigated the effects of NBP-14 in six different cancer cell lines, primary leukemia B-cells and normal B-cells. All cells tested expressed α7 nAChR, intracellular and extracellular T14...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28065843/alpha-7-nicotinic-agonists-for-cognitive-deficits-in-neuropsychiatric-disorders-a-translational-meta-analysis-of-rodent-and-human-studies
#2
Alan S Lewis, Gerrit I van Schalkwyk, Michael H Bloch
Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer's disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown...
January 5, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28039041/spinal-activation-of-alpha7-nicotinic-acetylcholine-receptor-attenuates-posttraumatic-stress-disorder-related-chronic-pain-via-suppression-of-glial-activation
#3
Rao Sun, Wei Zhang, Jinhua Bo, Zuoxia Zhang, Yishan Lei, Wenwen Huo, Yue Liu, Zhengliang Ma, Xiaoping Gu
The high prevalence of chronic pain in posttraumatic stress disorder (PTSD) individuals has been widely reported by clinical studies, which emphasized an urgent need to uncover the underlying mechanisms and identify potential therapeutic targets. Recent studies suggested that targeting activated glia and their pro-inflammatory products may provide a novel and effective therapy for the stress-related pain. In this study, we investigated whether activation of alpha-7 nicotinic acetylcholine receptor (α7 nAChR), a novel anti-inflammatory target, could attenuate PTSD-related chronic pain...
December 28, 2016: Neuroscience
https://www.readbyqxmd.com/read/27979692/therapeutic-potential-and-limitations-of-cholinergic-anti-inflammatory-pathway-in-sepsis
#4
REVIEW
Alexandre Kanashiro, Fabiane Sônego, Raphael G Ferreira, Fernanda V S Castanheira, Caio A Leite, Vanessa F Borges, Daniele C Nascimento, David F Cólon, José Carlos Alves-Filho, Luis Ulloa, Fernando Q Cunha
Sepsis is one of the main causes of mortality in hospitalized patients. Despite the recent technical advances and the development of novel generation of antibiotics, severe sepsis remains a major clinical and scientific challenge in modern medicine. Unsuccessful efforts have been dedicated to the search of therapeutic options to treat the deleterious inflammatory components of sepsis. Recent findings on neuronal networks controlling immunity raised expectations for novel therapeutic strategies to promote the regulation of sterile inflammation, such as autoimmune diseases...
December 12, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27914011/activation-of-alpha-7-nicotinic-acetylcholine-receptor-reduces-brain-edema-in-mice-with-ischemic-stroke-and-bone-fracture
#5
Dingquan Zou, Man Luo, Zhenying Han, Lei Zhan, Wan Zhu, Shuai Kang, Chen Bao, Zhao Li, Jeffrey Nelson, Rui Zhang, Hua Su
Stroke is an important risk factor for bone fracture. We showed previously that bone fracture at the acute stage of ischemic stroke worsens, and activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) improves, stroke recovery by attenuating inflammation. We hypothesized that activation of α-7 nAchR also improves the blood-brain barrier (BBB) integrity. Permanent distal middle cerebral artery occlusion (pMCAO) was performed on C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27835950/targeted-high-throughput-sequencing-of-candidate-genes-for-chronic-obstructive-pulmonary-disease
#6
Hans Matsson, Cilla Söderhäll, Elisabet Einarsdottir, Maxime Lamontagne, Sanna Gudmundsson, Helena Backman, Anne Lindberg, Eva Rönmark, Juha Kere, Don Sin, Dirkje S Postma, Yohan Bossé, Bo Lundbäck, Joakim Klar
BACKGROUND: Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD. METHODS: Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking...
November 11, 2016: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/27834303/single-nucleotide-polymorphisms-and-genotypes-of-transient-receptor-potential-ion-channel-and-acetylcholine-receptor-genes-from-isolated-b-lymphocytes-in-myalgic-encephalomyelitis-chronic-fatigue-syndrome-patients
#7
Sonya Marshall-Gradisnik, Samantha Johnston, Anu Chacko, Thao Nguyen, Peter Smith, Donald Staines
OBJECTIVE: The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca(2+)) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients...
November 10, 2016: Journal of International Medical Research
https://www.readbyqxmd.com/read/27766701/alpha-7-nicotinic-acetylcholine-receptor-nachr-agonist-inhibits-the-development-of-endometriosis-by-regulating-inflammation
#8
Kaori Yamada-Nomoto, Osamu Yoshino, Ikumi Akiyama, Akemi Ushijima, Yosuke Ono, Tomoko Shima, Akitoshi Nakashima, Shusaku Hayashi, Makoto Kadowaki, Yutaka Osuga, Shigeru Saito
OBJECTIVE: We investigated α-7 nAchR expression in human peritoneal macrophages and examined whether activation of nAchR might be a new therapy for endometriosis. MATERIALS AND METHODS: Human peritoneal fluid mononuclear cells (PFMC) were stimulated with lipopolysaccharide (LPS) in the presence of α-7 nAChR agonists. In a murine endometriosis model, α-7 nAChR modulators were administered. RESULTS: Human PFMC expressed α-7 nAChR at the mRNA and protein levels...
December 2016: American Journal of Reproductive Immunology: AJRI
https://www.readbyqxmd.com/read/27752155/-nicotine-alleviates-the-liver-inflammation-of-non-alcoholic-steatohepatitis-induced-by-high-fat-and-high-fructose-in-mice
#9
X M Chen, F Q Li, S Yan, X C Wu, C L Tang
OBJECTIVE: To investigate the anti-inflammation effects by activation of the cholinergic anti-inflammatory pathway and its mechanisms in non-alcoholic steatohepatitis (NASH) model mice. METHODS: 6-week-old male C57BL/6J (B6) mice were randomly divided into four groups: the first group was normal mice, injected with saline; the second group was normal mice, injected with nicotine; the third group was NASH model mice, injected with saline; the fourth group was NASH model mice, injected with nicotine...
October 18, 2016: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/27527585/prenatal-kynurenine-exposure-in-rats-age-dependent-changes-in-nmda-receptor-expression-and-conditioned-fear-responding
#10
Michelle L Pershing, David Phenis, Valentina Valentini, Ana Pocivavsek, Derick H Lindquist, Robert Schwarcz, John P Bruno
RATIONALE: Levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs) and antagonist at glutamatergic N-methyl-D-aspartate receptors (NMDARs), are elevated in the brain of patients with schizophrenia (SZ). In rats, dietary exposure to KYNA's immediate precursor kynurenine during the last week of gestation produces neurochemical and cognitive deficits in adulthood that resemble those seen in patients with SZ. OBJECTIVES: The present experiments examined whether prenatal kynurenine exposure results in age-dependent changes in the kynurenine pathway (KP), expression of selected receptors, and cognitive function...
October 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27488345/alpha-7-nicotinic-receptors-in-nervous-system-disorders-from-function-to-therapeutic-perspectives
#11
Marcella Reale, Ada Maria Tata
The α7 nicotinic receptor consists of identical subunits and is one of the most abundant acetylcholine receptor in the mammalian central nervous system. However its expression is also found in the peripheral nervous system as well as in the immune system and various peripheral tissues. Its function is involved in the regulation of a range of activities such as classical excitatory neurotransmission in some brain regions, modulation of the release of several neurotransmitters, regulation of neurite outgrowth, and even neuronal survival/death...
July 29, 2016: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27341335/vagotomy-affects-the-development-of-oral-tolerance-and-increases-susceptibility-to-develop-colitis-independently-of-the-alpha-7-nicotinic-receptor
#12
Martina Di Giovangiulio, Goele Bosmans, Elisa Meroni, Nathalie Stakenborg, Morgane Florens, Giovanna Farro, Pedro J Gomez-Pinilla, Gianluca Matteoli, Guy Boeckxstaens
Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR(-/-) mice...
June 14, 2016: Molecular Medicine
https://www.readbyqxmd.com/read/27323436/-effects-of-electroaupuncture-stimulation-of-xiajuxu-st-39-etc-on-duodenal-mucosal-injury-serum-pro-inflammatory-factors-levels-and-duodenal-nicotinic-acetylcholine-receptor-alpha-7-expression-in-duodenal-ulcer-rats
#13
Xi Ling, Hong Zhang, Xi-qin Yi, Jin-feng Wu
OBJECTIVE: To observe the relatively specific effect of electroacupuncture (EA) of "Xiajuxu" (ST 39, the lower hesea paint of the small intestine), etc. on the level of serum TNF-alpha, lnterleukin-1 P (IL-1 P) and high mobility group protein B 1 (HMGB 1) contents, and duodenum a7 nicotinic acetyicholine receptor (nAchR) expression in duodenal ulcer rats, so as to explore its mechanisms underlying improving duodenal ulcer. METHODS: Sixty SD rats were randomly divided into 6 groups: normal control, model, Xiajuxu (ST 39), Zusanli (ST 36), Shangjuxu (ST 37) and Yanglingquan (GB 34)...
April 2016: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/27256075/nicotine-inhibits-activation-of-microglial-proton-currents-via-interactions-with-%C3%AE-7-acetylcholine-receptors
#14
Mami Noda, A I Kobayashi
Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine, though little is known about the mechanism. Here we show that nicotine inhibits lipopolysaccharide (LPS)-induced proton (H(+)) currents and morphological change by using primary cultured microglia. The H(+) channel currents were measured by whole-cell patch clamp method under voltage-clamp condition...
January 2017: Journal of Physiological Sciences: JPS
https://www.readbyqxmd.com/read/27252943/dehydration-and-cognition-in-geriatrics-a-hydromolecular-hypothesis
#15
Adonis Sfera, Michael Cummings, Carolina Osorio
Dehydration is one of the ten most frequent diagnoses responsible for the hospital admission of elderly in the United States. It is associated with increased mortality, morbidity and an estimated cost of 1.14 billion per year (Xiao et al., 2004; Schlanger et al., 2010; Pretorius et al., 2013; Frangeskou et al., 2015). Older individuals are predisposed to dehydration encephalopathy as a result of decreased total body water (TBW) and diminished sensation of thirst. We hypothesize that thirst blunting in older individuals is the result of a defective microRNA-6842-3p failing to silence the expression of the vesicular GABA transporters (VGAT) and alpha 7 cholinergic nicotinic receptors in the subfornical organ (SFO) of the hypothalamus...
2016: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/27186239/investigating-the-effects-of-copy-number-variants-on-reading-and-language-performance
#16
Alessandro Gialluisi, Alessia Visconti, Erik G Willcutt, Shelley D Smith, Bruce F Pennington, Mario Falchi, John C DeFries, Richard K Olson, Clyde Francks, Simon E Fisher
BACKGROUND: Reading and language skills have overlapping genetic bases, most of which are still unknown. Part of the missing heritability may be caused by copy number variants (CNVs). METHODS: In a dataset of children recruited for a history of reading disability (RD, also known as dyslexia) or attention deficit hyperactivity disorder (ADHD) and their siblings, we investigated the effects of CNVs on reading and language performance. First, we called CNVs with PennCNV using signal intensity data from Illumina OmniExpress arrays (~723,000 probes)...
2016: Journal of Neurodevelopmental Disorders
https://www.readbyqxmd.com/read/27167578/alpha-7-nicotinic-receptor-coupling-to-heterotrimeric-g-proteins-modulates-rhoa-activation-cytoskeletal-motility-and-structural-growth
#17
Justin R King, Nadine Kabbani
Nicotinic acetylcholine receptors (nAChRs) modulate the growth and structure of neurons throughout the nervous system. Ligand stimulation of the α7 nAChR has been shown to regulate the large heterotrimeric GTP-binding protein (G protein) signaling in various types of cells. Here, we demonstrate a role for α7 nAChR/G protein interaction in the activation of the small (monomeric) RhoA GTPase leading to cytoskeletal changes during neurite growth. Treatment of PC12 cells with the α7 nAChR agonist choline or PNU-282987 was associated with an increase in RhoA activity and an inhibition in neurite growth...
August 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27154173/effects-of-alpha-7-nicotinic-acetylcholine-receptor-positive-allosteric-modulator-on-lipopolysaccharide-induced-neuroinflammatory-pain-in-mice
#18
Muzaffar Abbas, Shafiqur Rahman
Evidence indicates that microglial activation contributes to the pathophysiology and maintenance of neuroinflammatory pain involving central nervous system alpha-7 nicotinic acetylcholine receptors. The objective of the present study was to determine the effects of 3a,4,5,9b-Tetrahydro-4-(1-naphthalenyl)-3H-cyclopentan[c]quinoline-8-sulfonamide (TQS), an alpha-7 nicotinic acetylcholine receptor positive allosteric modulator (PAM), on tactile allodynia and thermal hyperalgesia following lipopolysaccharide (LPS)-induced microglial activation in hippocampus, a neuroinflammatory pain model in mice...
July 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27117524/a-crispr-cas9-mediated-point-mutation-in-the-alpha-6-subunit-of-the-nicotinic-acetylcholine-receptor-confers-resistance-to-spinosad-in-drosophila-melanogaster
#19
Christoph T Zimmer, William T Garrood, A Mirel Puinean, Manuela Eckel-Zimmer, Martin S Williamson, T G Emyr Davies, Chris Bass
Spinosad, a widely used and economically important insecticide, targets the nicotinic acetylcholine receptor (nAChRs) of the insect nervous system. Several studies have associated loss of function mutations in the insect nAChR α6 subunit with resistance to spinosad, and in the process identified this particular subunit as the specific target site. More recently a single non-synonymous point mutation, that does not result in loss of function, was identified in spinosad resistant strains of three insect species that results in an amino acid substitution (G275E) of the nAChR α6 subunit...
June 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27085880/evidence-for-association-between-low-frequency-variants-in-chrna6-chrnb3-and-antisocial-drug-dependence
#20
Helen M Kamens, Robin P Corley, Phillip A Richmond, Todd M Darlington, Robin Dowell, Christian J Hopfer, Michael C Stallings, John K Hewitt, Sandra A Brown, Marissa A Ehringer
Common SNPs in nicotinic acetylcholine receptor genes (CHRN genes) have been associated with drug behaviors and personality traits, but the influence of rare genetic variants is not well characterized. The goal of this project was to identify novel rare variants in CHRN genes in the Center for Antisocial Drug Dependence (CADD) and Genetics of Antisocial Drug Dependence (GADD) samples and to determine if low frequency variants are associated with antisocial drug dependence. Two samples of 114 and 200 individuals were selected using a case/control design including the tails of the phenotypic distribution of antisocial drug dependence...
September 2016: Behavior Genetics
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