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https://www.readbyqxmd.com/read/29682193/competitive-docking-model-for-prediction-of-the-human-nicotinic-acetylcholine-receptor-%C3%AE-7-binding-of-tobacco-constituents
#1
Hui Wen Ng, Carmine Leggett, Sugunadevi Sakkiah, Bohu Pan, Hao Ye, Leihong Wu, Chandrabose Selvaraj, Weida Tong, Huixiao Hong
The detrimental health effects associated with tobacco use constitute a major public health concern. The addiction associated with nicotine found in tobacco products has led to difficulty in quitting among users. Nicotinic acetylcholine receptors (nAChRs) are the targets of nicotine and are responsible for addiction to tobacco products. However, it is unknown if the other >8000 tobacco constituents are addictive. Since it is time-consuming and costly to experimentally assess addictive potential of such larger number of chemicals, computationally predicting human nAChRs binding is important for in silico evaluation of addiction potential of tobacco constituents and needs structures of human nAChRs...
March 30, 2018: Oncotarget
https://www.readbyqxmd.com/read/29681847/cholinergic-hypofunction-in-presbycusis-related-tinnitus-with-cognitive-function-impairment-emerging-hypotheses
#2
Qingwei Ruan, Zhuowei Yu, Weibin Zhang, Jian Ruan, Chunhui Liu, Ruxin Zhang
Presbycusis (age-related hearing loss) is a potential risk factor for tinnitus and cognitive deterioration, which result in poor life quality. Presbycusis-related tinnitus with cognitive impairment is a common phenotype in the elderly population. In these individuals, the central auditory system shows similar pathophysiological alterations as those observed in Alzheimer's disease (AD), including cholinergic hypofunction, epileptiform-like network synchronization, chronic inflammation, and reduced GABAergic inhibition and neural plasticity...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29679680/ns6740-an-%C3%AE-7-nicotinic-acetylcholine-receptor-silent-agonist-disrupts-hippocampal-synaptic-plasticity
#3
Roger L Papke, Can Peng, Ashok Kumar, Clare Stokes
Long-term potentiation (LTP) in the dentate gyrus was previously shown to be enhanced by nicotine, an effect dependent on both homomeric α7 and heteromeric α2β2 nicotinic acetylcholine receptors (nAChR). In our experiments, bath-applied nicotine produced no significant enhancement of LTP. The α7 nAChR silent agonist NS6740, a weak activator of α7 nAChR ion channels but an effective modulator of the cholinergic anti-inflammatory pathway, decreased LTP and, additionally, produced a substantial reduction in the baseline synaptic function prior to the high frequency stimulation used to induce LTP...
April 18, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29678746/thirdhand-smoke-component-can-exacerbate-a-mouse-asthma-model-via-mast-cells
#4
Mang Yu, Kaori Mukai, Mindy Tsai, Stephen J Galli
BACKGROUND: Thirdhand smoke (THS) represents the accumulation of secondhand smoke on indoor surfaces and in dust, which, over time, can become more toxic than secondhand smoke. Although it is well known that children of smokers are at increased risk for developing asthma and for exacerbation of that disease if they already have it, how exposure to THS may influence the development or exacerbation of asthma remains unknown. OBJECTIVE: We investigated whether epicutaneous exposure to an important component of THS, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), can influence asthma pathology in a model elicited in mice by repeated intranasal challenge with cockroach antigen (CRA)...
April 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29678590/comparlow-arsenic-concentrations-impair-memory-in-rat-offpring-exposed-during-pregnancy-and-lactation-role-of-%C3%AE-7-nicotinic-receptor-glutamate-and-oxidative-stress
#5
Nina María Mónaco, Mariana Bartos, Sergio Dominguez, Cristina Gallegos, Cristina Bras, María Del Carmen Esandi, Cecilia Bouzat, Leda Giannuzzi, Alejandra Minetti, Fernanda Gumilar
Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Arsenic exposure has been associated to cognitive deficits. However, the underlying mechanisms remain unknown. In the present work we investigated in female adult offspring the effect of the exposure to low arsenite sodium levels through drinking water during pregnancy and lactation on short- and long-term memory. We also considered a possible underlying neurotoxic mechanism. Pregnant rats were exposed during pregnancy and lactation to environmentally relevant iAs concentrations (0...
April 17, 2018: Neurotoxicology
https://www.readbyqxmd.com/read/29677582/maternal-nicotine-exposure-effects-on-adolescent-learning-and-memory-are-abolished-in-alpha-%C3%AE-2-nicotinic-acetylcholine-receptor-null-mutant-mice
#6
Celina Mojica, Yu Bai, Shahrdad Lotfipour
The objective of the current study is to test the hypothesis that the deletion of alpha(α)2* nicotinic acetylcholine receptors (nAChRs) (encoded by the Chrna2 gene) ablate maternal nicotine-induced learning and memory deficits in adolescent mice. We use a pre-exposure-dependent contextual fear conditioning behavioral paradigm that is highly hippocampus-dependent. Adolescent wild type and α2-null mutant offspring are exposed to vehicle or maternal nicotine exposure (200 μg/ml, expressed as base) in the drinking water throughout pregnancy until weaning...
April 9, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29672680/cognitive-correlates-of-%C3%AE-4%C3%AE-2-nicotinic-acetylcholine-receptors-in-mild-alzheimer-s-dementia
#7
Osama Sabri, Philipp M Meyer, Susanne Gräf, Swen Hesse, Stephan Wilke, Georg-Alexander Becker, Michael Rullmann, Marianne Patt, Julia Luthardt, Gudrun Wagenknecht, Alexander Hoepping, Rene Smits, Annegret Franke, Bernhard Sattler, Solveig Tiepolt, Steffen Fischer, Winnie Deuther-Conrad, Ulrich Hegerl, Henryk Barthel, Peter Schönknecht, Peter Brust
In early Alzheimer's dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer's dementia...
April 17, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29671814/sex-specific-alterations-in-%C3%AE-4-nicotinic-receptor-expression-in-the-nucleus-accumbens
#8
Joan Y Holgate, Josephine R Tarren, Selena E Bartlett
Background : The mechanisms leading from traumatic stress to social, emotional and cognitive impairment and the development of mental illnesses are still undetermined and consequently there remains a critical need to develop therapies for preventing the adverse consequences of traumatic stress. Research indicates nicotinic acetylcholine receptors containing α4 subunits (α4*nAChRs) are both impacted by stress and capable of modulating the stress response. In this study, we investigated whether varenicline, a partial α4β2*nAChR agonist which reduces nicotine, alcohol and sucrose consumption, can reduce stress, a driving factor in substance use disorders...
April 19, 2018: Brain Sciences
https://www.readbyqxmd.com/read/29667304/inhibition-of-alpha7-nicotinic-receptors-in-the-ventral-hippocampus-selectively-attenuates-reinstatement-of-morphine-conditioned-place-preference-and-associated-changes-in-ampa-receptor-binding
#9
Victoria L Wright, Polymnia Georgiou, Alexis Bailey, David J Heal, Christopher P Bailey, Susan Wonnacott
Recurrent relapse is a major problem in treating opiate addiction. Pavlovian conditioning plays a role in recurrent relapse whereby exposure to cues learned during drug intake can precipitate relapse to drug taking. α7 nicotinic acetylcholine receptors (nAChRs) have been implicated in attentional aspects of cognition and mechanisms of learning and memory. In this study we have investigated the role of α7 nAChRs in morphine-conditioned place preference (morphine-CPP). CPP provides a model of associative learning that is pertinent to associative aspects of drug dependence...
April 17, 2018: Addiction Biology
https://www.readbyqxmd.com/read/29666375/association-and-cis-mqtl-analysis-of-variants-in-chrna3-a5-chrna7-chrnb2-and-chrnb4-in-relation-to-nicotine-dependence-in-a-chinese-han-population
#10
Qiang Liu, Haijun Han, Maiqiu Wang, Yinghao Yao, Li Wen, Keran Jiang, Yunlong Ma, Rongli Fan, Jiali Chen, Kunkai Su, Zhongli Yang, Wenyan Cui, Wenji Yuan, Xianzhong Jiang, Jingjing Li, Thomas J Payne, Jundong Wang, Ming D Li
Nicotine dependence (ND) is a worldwide health problem. Numerous genetic studies have demonstrated a significant association of variants in nicotinic acetylcholine receptors (nAChRs) with smoking behaviors. However, most of these studies enrolled only subjects of European or African ancestry. In addition, although an increasing body of evidence implies a causal connection of single-nucleotide polymorphisms (SNPs) and epigenetic regulation of gene expression, few studies of this issue have been reported. In this study, we performed both association and interaction analysis for 67 SNPs in CHRNA3-A5, CHRNA7, CHRNB2, and CHRNB4 with ND in a Chinese Han population (N = 5055)...
April 18, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29665406/sn56-neuronal-cell-death-after-24-h-and-14-days-chlorpyrifos-exposure-through-glutamate-transmission-dysfunction-increase-of-gsk-3%C3%AE-enzyme-%C3%AE-amyloid-and-tau-protein-levels
#11
Paula Moyano, María Teresa Frejo, María José Anadon, José Manuel García, María Jesús Díaz, Margarita Lobo, Emma Sola, Jimena García, Javier Del Pino
Chlorpyrifos (CPF) is an organophosphate insecticide described to induce cognitive disorders, both after acute and repeated administration. However, the mechanisms through which it induces these effects are unknown. CPF has been reported to produce basal forebrain cholinergic neuronal cell death, involved on learning and memory regulation, which could be the cause of such cognitive disorders. Neuronal cell death was partially mediated by oxidative stress generation, P75NTR and α7 -nAChRs gene expression alteration triggered through acetylcholinesterase (AChE) variants disruption, suggesting other mechanisms are involved...
April 14, 2018: Toxicology
https://www.readbyqxmd.com/read/29663646/isobaric-tag-based-protein-profiling-of-a-nicotine-treated-alpha7-nicotinic-receptor-null-human-haploid-cell-line
#12
Joao A Paulo, Steven P Gygi
Nicotinic acetylcholine receptors (nAChR), the primary cell surface targets of nicotine, have implications in various neurological disorders. Here we investigate the proteome-wide effects of nicotine on human haploid cell lines (wildtype HAP1 and α7KO-HAP1) to address differences in nicotine-induced protein abundance profiles between these cell lines. We performed an SPS-MS3-based TMT10-plex experiment arranged in a 2-3-2-3 design with two replicates for the untreated samples and three for the treated samples for each cell line...
April 16, 2018: Proteomics
https://www.readbyqxmd.com/read/29663387/muscarinic-and-nicotinic-acetylcholine-receptor-agonists-current-scenario-in-alzheimer-s-disease-therapy
#13
REVIEW
Stuti Verma, Ashwini Kumar, Timir Tripathi, Awanish Kumar
OBJECTIVES: Alzheimer's disease (AD) has become the primary cause of dementia. It shows a progressive cognitive dysfunction with degenerating neurons. Acetylcholine receptors (AChRs) propagate the cognitive ability and it consists of two primary members namely muscarinic (mAChRs) and nicotinic receptors (nAChRs). Where mAChRs is G-protein coupled receptor, (nAChRs) are ligand-gated ion channels. The conventional therapeutic regimen for AD consists of three acetylcholinestearse inhibitors while a single NMDA receptor antagonist...
April 16, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29661886/distinct-in-vivo-roles-of-secreted-app-ectodomain-variants-apps%C3%AE-and-apps%C3%AE-in-regulation-of-spine-density-synaptic-plasticity-and-cognition
#14
Max C Richter, Susann Ludewig, Alex Winschel, Tobias Abel, Charlotte Bold, Leonie R Salzburger, Susanne Klein, Kang Han, Sascha W Weyer, Ann-Kristina Fritz, Bodo Laube, David P Wolfer, Christian J Buchholz, Martin Korte, Ulrike C Müller
Increasing evidence suggests that synaptic functions of the amyloid precursor protein (APP), which is key to Alzheimer pathogenesis, may be carried out by its secreted ectodomain (APPs). The specific roles of APPsα and APPsβ fragments, generated by non-amyloidogenic or amyloidogenic APP processing, respectively, remain however unclear. Here, we expressed APPsα or APPsβ in the adult brain of conditional double knockout mice (cDKO) lacking APP and the related APLP2. APPsα efficiently rescued deficits in spine density, synaptic plasticity (LTP and PPF), and spatial reference memory of cDKO mice...
April 16, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29661129/spidr-small-molecule-peptide-influenced-drug-repurposing
#15
Matthew D King, Thomas Long, Daniel L Pfalmer, Timothy L Andersen, Owen M McDougal
BACKGROUND: Conventional de novo drug design is costly and time consuming, making it accessible to only the best resourced research organizations. An emergent approach to new drug development is drug repurposing, in which compounds that have already gone through some level of clinical testing are examined for efficacy against diseases divergent than their original application. Repurposing of existing drugs circumvents the time and considerable cost of early stages of drug development, and can be accelerated by using software to screen existing chemical databases to identify suitable drug candidates...
April 16, 2018: BMC Bioinformatics
https://www.readbyqxmd.com/read/29660616/intestinal-damage-neurotoxicity-and-biochemical-responses-caused-by-tris-2-chloroethyl-phosphate-and-tricresyl-phosphate-on-earthworm
#16
Yang Yang, Yao Xiao, Yeqian Chang, Yibin Cui, Göran Klobučar, Mei Li
Organophosphate esters (OPEs) draw growing concern about characterizing the potential risk on environmental health due to its wide usage and distribution. Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl) phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify the effects and potential mechanism of their toxicity...
April 13, 2018: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/29642561/%C3%AE-nicotinamide-adenine-dinucleotide-%C3%AE-nad-inhibits-atp-dependent-il-1%C3%AE-release-from-human-monocytic-cells
#17
Sebastian Daniel Hiller, Sarah Heldmann, Katrin Richter, Innokentij Jurastow, Mira Küllmar, Andreas Hecker, Sigrid Wilker, Gabriele Fuchs-Moll, Ivan Manzini, Günther Schmalzing, Wolfgang Kummer, Winfried Padberg, J Michael McIntosh, Jelena Damm, Anna Zakrzewicz, Veronika Grau
While interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine essential for host defense, high systemic levels cause life-threatening inflammatory syndromes. ATP, a stimulus of IL-1β maturation, is released from damaged cells along with β-nicotinamide adenine dinucleotide (β-NAD). Here, we tested the hypothesis that β-NAD controls ATP-signaling and, hence, IL-1β release. Lipopolysaccharide-primed monocytic U937 cells and primary human mononuclear leukocytes were stimulated with 2'(3')- O -(4-benzoyl-benzoyl)ATP trieethylammonium salt (BzATP), a P2X7 receptor agonist, in the presence or absence of β-NAD...
April 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29628323/synthesis-and-radiofluorination-of-novel-fluoren-9-one-based-derivatives-for-the-imaging-of-%C3%AE-7-nicotinic-acetylcholine-receptor-with-pet
#18
Rodrigo Teodoro, Matthias Scheunemann, Barbara Wenzel, Dan Peters, Winnie Deuther-Conrad, Peter Brust
By structure-activity relationship studies on the tilorone scaffold, the 'one armed' substituted dibenzothiophenes and the fluoren-9-ones were identified as the most potential α7 nAChR ligands. While the suitability of dibenzothiophene derivatives as PET tracers is recognized, the potential of fluoren-9-ones is insufficiently investigated. We herein report on a series of fluoren-9-one based derivatives targeting α7 nAChR with compounds 8a and 8c possessing the highest affinity and selectivity. Accordingly, with [18 F]8a and [18 F]8c we designed and initially evaluated the first fluoren-9-one derived α7 nAChR selective PET ligands...
March 29, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29626299/short-chain-consensus-alpha-neurotoxin-a-synthetic-60-mer-peptide-with-generic-traits-and-enhanced-immunogenic-properties
#19
Guillermo de la Rosa, Ligia L Corrales-García, Ximena Rodriguez-Ruiz, Estuardo López-Vera, Gerardo Corzo
The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx...
April 6, 2018: Amino Acids
https://www.readbyqxmd.com/read/29621993/cholinergic-receptor-nicotinic-alpha-5-subunit-polymorphisms-are-associated-with-smoking-cessation-success-in-women
#20
Paulo Roberto Xavier Tomaz, Juliana Rocha Santos, Jaqueline Scholz, Tânia Ogawa Abe, Patrícia Viviane Gaya, André Brooking Negrão, José Eduardo Krieger, Alexandre Costa Pereira, Paulo Caleb Júnior Lima Santos
BACKGROUND: The identification of variants in the nicotinic acetylcholine receptor (nAChR) subunit genes associated with smoking phenotypes are increasingly important for prevention and treatment of nicotine dependence. In the context of personalized medicine, the aims of this study were to evaluate whether cholinergic receptor nicotinic alpha 2 (CHRNA2), cholinergic receptor nicotinic alpha 3 (CHRNA3), cholinergic receptor nicotinic alpha 5 (CHRNA5) and cholinergic receptor nicotinic beta 3 (CHRNB3) polymorphisms were associated with nicotine dependence severity, and to investigate possible pharmacogenetics markers of smoking cessation treatment...
April 5, 2018: BMC Medical Genetics
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