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https://www.readbyqxmd.com/read/29768467/alpha-7-nicotinic-receptors-attenuate-neurite-development-through-calcium-activation-of-calpain-at-the-growth-cone
#1
Justin R King, Nadine Kabbani
The α7 nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that plays an important role in cellular calcium signaling contributing to synaptic development and plasticity, and is a key drug target for the treatment of neurodegenerative conditions such as Alzheimer's disease. Here we show that α7 nAChR mediated calcium signals in differentiating PC12 cells activate the proteolytic enzyme calpain leading to spectrin breakdown, microtubule retraction, and attenuation in neurite growth. Imaging in growth cones confirms that α7 activation decreases EB3 comet motility in a calcium dependent manner as demonstrated by the ability of α7 nAChR, ryanodine, or IP3 receptor antagonists to block the effect of α7 nAChR on growth...
2018: PloS One
https://www.readbyqxmd.com/read/29722329/alpha-7-nicotinic-acetylcholine-receptor-agonist-treatment-in-a-rat-model-of-huntington-s-disease-and-involvement-of-heme-oxygenase-1
#2
Laura Foucault-Fruchard, Claire Tronel, Sylvie Bodard, Zuhal Gulhan, Julie Busson, Sylvie Chalon, Daniel Antier
Neuroinflammation is a common element involved in the pathophysiology of neurodegenerative diseases. We recently reported that repeated alpha-7 nicotinic acetylcholine receptor (α7nAChR) activations by a potent agonist such as PHA 543613 in quinolinic acid-injured rats exhibited protective effects on neurons. To further investigate the underlying mechanism, we established rat models of early-stage Huntington's disease by injection of quinolinic acid into the right striatum and then intraperitoneally injected 12 mg/kg PHA 543613 or sterile water, twice a day during 4 days...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29572553/galantamine-anti-colitic-effect-role-of-alpha-7-nicotinic-acetylcholine-receptor-in-modulating-jak-stat3-nf-%C3%AE%C2%BAb-hmgb1-rage-and-p-akt-bcl-2-pathways
#3
Shakeeb A Wazea, Walaa Wadie, Ashraf K Bahgat, Hanan S El-Abhar
Vagal stimulation controls systemic inflammation and modulates the immune response in different inflammatory conditions, including inflammatory bowel diseases (IBD). The released acetylcholine binds to alpha-7 nicotinic acetylcholine receptor (α7 nAChR) to suppress pro-inflammatory cytokines. This provides a new range of potential therapeutic approaches for controlling inflammatory responses. The present study aimed to assess whether galantamine (Galan) anti-inflammatory action involves α7 nAChR in a 2,4,6-trinitrobenzene sulfonic acid (TNBS) model of colitis and to estimate its possible molecular pathways...
March 23, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29566578/aminobenzisoxazole-compounds-as-agonists-of-%C3%AE-7-nicotinic-acetylcholine-receptors-a-patent-evaluation-wo-2017027600
#4
Yang He, Jingshan Shen
alpha 7 subtype nicotinic acetylcholine receptor (α7 nAChR) ligands, that is, ligands that interact with the orthosteric or allosteric binding sites of α7 nAChR, hold great potential for several therapeutic applications. Numerous compounds have been designed targeting α7 nAChR but most of them cannot be used therapeutically for various reasons. Areas covered: The patent application describes a series of germinal substituted aminobenzisoxazole compounds as α7 nAChR ligands. These compounds were claimed as potential therapeutics for treating and/or improving cognitive function...
March 23, 2018: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29516284/stimulation-of-ace2-ang-1-7-mas-axis-by-diminazene-ameliorates-alzheimer-s-disease-in-the-d-galactose-ovariectomized-rat-model-role-of-pi3k-akt-pathway
#5
Ahmed S Kamel, Noha F Abdelkader, Sahar S Abd El-Rahman, Marwan Emara, Hala F Zaki, Mahmoud M Khattab
Overactivation of angiotensin-converting enzyme/angiotensin 2/angiotensin receptor-1 (ACE/Ang2/AT1) axis provokes amyloid-β-induced apoptosis and neurodegeneration in Alzheimer's disease (AD). Moreover, activation of AT1 impairs the survival pathway phosphoinositide 3-kinase/protein kinase B (PI3K/Akt). Interestingly, the coupling between ACE2/Ang(1-7)/Mas receptor (MasR) axis and PI3K/Akt activation opposes AT1-induced apoptosis. However, the effect of in vivo stimulation of MasR against AD and its correlation to PI3K/Akt is not yet elucidated...
March 7, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29501575/orally-administered-nicotine-effects-on-rat-urinary-bladder-proliferation-and-carcinogenesis
#6
Shugo Suzuki, Samuel M Cohen, Lora L Arnold, Hiroyuki Kato, Satoshi Fuji, Karen L Pennington, Yuko Nagayasu, Aya Naiki-Ito, Yoriko Yamashita, Satoru Takahashi
Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. Cigarette smoke inhalation in mice and orally administered nicotine in rats and mice increased urothelial cell proliferation. Nicotine, a major component of smoke, induced cell proliferation in multiple cell types in vitro. In the present study, the enhancing effects of nicotine on F344 rat bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Nicotine administered in drinking water for 32 weeks following 4 weeks of BBN treatment significantly increased the incidence and number of urothelial carcinomas dose-dependently...
April 1, 2018: Toxicology
https://www.readbyqxmd.com/read/29501534/functional-evidence-for-the-inflammatory-reflex-in-teleosts-a-novel-%C3%AE-7-nicotinic-acetylcholine-receptor-modulates-the-macrophage-response-to-dsrna
#7
Débora Torrealba, Joan Carles Balasch, Manuel Criado, Lluís Tort, Simon Mackenzie, Nerea Roher
The inflammatory reflex modulates the innate immune system, keeping in check the detrimental consequences of overstimulation. A key player controlling the inflammatory reflex is the alpha 7 acetylcholine receptor (α7nAChR). This receptor is one of the signalling molecules regulating cytokine expression in macrophages. In this study, we characterize a novel teleost α7nAChR. Protein sequence analysis shows a high degree of conservation with mammalian orthologs and trout α7nAChR has all the features and essential amino acids to form a fully functional receptor...
July 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29459050/n-methyl-d-aspartate-type-glutamate-receptor-modulators-and-related-medications-for-the-enhancement-of-auditory-system-plasticity-in-schizophrenia
#8
Joshua T Kantrowitz
Deficits in N-methyl-d-aspartate-type (NMDAR) function contribute to cognitive deficits in schizophrenia, particularly dysfunction in neuroplasticity, defined as reduced learning during training on exercises that place implicit, increasing demands on early sensory (auditory and visual) information processing. Auditory mismatch negativity (MMN) can be both a target engagement biomarker for the NMDAR and a proxy measure of neurophysiological plasticity. This review covers the evidence for using NMDAR modulator and related compounds for enhancement of cognition, with a particular focus on early auditory processing/plasticity...
February 17, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29406991/a-new-etiologic-model-for-alzheimers-disease
#9
Kathryn A Schiel
This etiologic model proposes that Alzheimers Disease (AD) arises when an unusually rapid increase in ventricle volume triggers axon stretch that culminates in the physical separation of trans-synaptic proteins. As a result, these proteins, such as neurexin, neuroligin, N-Cadherin and Amyloid Precursor Protein (APP), experience a change in the configuration of their cytoplasmic tail, so that instead of transmitting signals to create and maintain synaptic structure they activate enzymes, and generate molecules, that stimulate neurite growth; for example, the transformation of the N-Cadherin tail dissolves its complex with presenilin and β-catenin triggering activation of glycogen synthase kinase 3 beta (GSK3β) and cytoskeletal disruption...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29367088/sinomenine-inhibits-fibroblast-like-synoviocyte-proliferation-by-regulating-%C3%AE-7nachr-expression-via-erk-egr-1-pathway
#10
Lang Yi, Yan-Jun Lyn, Chong Peng, Rui-Li Zhu, Sha-Sha Bai, Liang Liu, Pei-Xun Wang, Hua Zhou, Yan Dong
Fibroblast like synoviocyte (FLS) is a crucial in the pathogenesis of rheumatoid arthritis (RA), and involved in inflammation and joint destruction. Sinomenine (SIN), an alkaloid derived from the plant Sinomenium acutum, has anti-inflammatory and analgesic effect and been used for RA treatment in China. Alpha 7 nicotinic acetylcholine receptors (α7nAChR), as the key receptor in cholinergic anti-inflammatory pathway (CAP) to inhibit inflammation, has been detected in RA patients synovium, but its role is still unclear...
March 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29261656/nicotinic-alpha-7-receptor-agonists-evp-6124-and-bms-933043-attenuate-scopolamine-induced-deficits-in-visuo-spatial-paired-associates-learning
#11
Michael R Weed, Joseph Polino, Laura Signor, Mark Bookbinder, Deborah Keavy, Yulia Benitex, Daniel G Morgan, Dalton King, John E Macor, Robert Zaczek, Richard Olson, Linda J Bristow
Agonists at the nicotinic acetylcholine alpha 7 receptor (nAChR α7) subtype have the potential to treat cognitive deficits in patients with Alzheimer's disease (AD) or schizophrenia. Visuo-spatial paired associates learning (vsPAL) is a task that has been shown to reliably predict conversion from mild cognitive impairment to AD in humans and can also be performed by nonhuman primates. Reversal of scopolamine-induced impairment of vsPAL performance may represent a translational approach for the development of nAChR α7 agonists...
2017: PloS One
https://www.readbyqxmd.com/read/29185480/initial-cross-over-test-of-a-positive-allosteric-modulator-of-alpha-7-nicotinic-receptors-to-aid-cessation-in-smokers-with-or-without-schizophrenia
#12
Kenneth A Perkins, K N Roy Chengappa, Joshua L Karelitz, Margaret C Boldry, Valerie Michael, Taylor Herb, Jessica Gannon, Jaspreet Brar, Lisa Ford, Stefanie Rassnick, Darlene H Brunzell
Preclinical research shows that compounds acting at α7 nicotinic receptors (nAChRs) can reduce nicotine self-administration, suggesting that a positive allosteric modulator (PAM) of α7 receptors, JNJ-39393406, may aid smoking cessation. Moreover, individuals with schizophrenia, who have very high rates of smoking, have reduced expression of α7 nAChRs and may particularly benefit from this compound. In two parallel studies using a within-subject cross-over design, 36 healthy smokers (Study 1) and 62 smokers with schizophrenia (Study 2), both groups high in quit interest, attempted to initiate quitting temporarily during each of two 3-week phases...
November 29, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29159020/the-current-agonists-and-positive-allosteric-modulators-of-%C3%AE-7-nachr-for-cns-indications-in-clinical-trials
#13
REVIEW
Taoyi Yang, Ting Xiao, Qi Sun, Kewei Wang
The alpha-7 nicotinic acetylcholine receptor ( α 7 nAChR), consisting of homomeric α 7 subunits, is a ligand-gated Ca2+ -permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α 7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia. Currently, a number of α 7 nAChR modulators have been reported and several of them have advanced into clinical trials...
November 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29117258/lung-epithelial-response-to-cigarette-smoke-and-modulation-by-the-nicotinic-alpha-7-receptor
#14
Lorise C Gahring, Elizabeth J Myers, Diane M Dunn, Robert B Weiss, Scott W Rogers
Cigarette smoking (CS) is a principal contributor to a spectrum of devastating lung diseases whose occurrence and severity may vary between individuals and not appear for decades after prolonged use. One explanation for the variability and delay in disease onset is that nicotine, the addictive component of CS, acts through the ionotropic nicotinic acetylcholine receptor (nAChR) alpha7 (α7) to modulate anti-inflammatory protection. In this study we measured the impact α7 signaling has on the mouse distal lung response to side-stream CS exposure for mice of the control genotype (α7G) and those in which the α7-receptor signaling mechanisms are restricted by point mutation (α7E260A:G)...
2017: PloS One
https://www.readbyqxmd.com/read/29114569/cholinergic-receptor-alterations-in-the-cerebral-cortex-of-spinal-cord-injured-rat
#15
R Chinthu, T R Anju, C S Paulose
Many areas of the cerebral cortex process sensory information or coordinate motor output necessary for control of movement. Disturbances in cortical cholinergic system can affect locomotor coordination. Spinal cord injury causes severe motor impairment and disturbances in cholinergic signalling can aggravate the situation. Considering the impact of cortical cholinergic firing in locomotion, we focussed the study in understanding the cholinergic alterations in cerebral cortex during spinal cord injury. The gene expression of key enzymes in cholinergic pathway - acetylcholine esterase and choline acetyl transferase showed significant upregulation in the cerebral cortex of spinal cord injured group compared to control with the fold increase in expression of acetylcholine esterase prominently higher than cholineacetyl transferase...
July 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29114104/bidirectional-regulation-of-aggression-in-mice-by-hippocampal-alpha-7-nicotinic-acetylcholine-receptors
#16
Alan S Lewis, Steven T Pittenger, Yann S Mineur, Dawson Stout, Philip H Smith, Marina R Picciotto
Humans with 15q13.3 microdeletion syndrome (15q13.3DS) are typically hemizygous for CHRNA7, the gene coding for the α7 nicotinic acetylcholine receptor (nAChR), and manifest a variable neuropsychiatric phenotype that frequently includes persistent aggression. In mice, nAChR activation by nicotine is anti-aggressive, or 'serenic,' an effect which requires α7 nAChRs and is recapitulated by GTS-21, an α7 nAChR partial agonist. Pharmacotherapies potentiating α7 nAChR signaling have also been shown to reduce aggression in human 15q13...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29089979/therapeutic-potential-of-%C3%AE-7-nicotinic-receptor-agonists-to-regulate-neuroinflammation-in-neurodegenerative-diseases
#17
REVIEW
Laura Foucault-Fruchard, Daniel Antier
Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases, are all characterized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29066952/the-sleep-wake-cycle-in-the-nicotinic-alpha-9-acetylcholine-receptor-subunit-knock-out-mice
#18
Natalia Madrid-López, Jorge Estrada, Javier Díaz, Alejandro Bassi, Paul H Délano, Adrián Ocampo-Garcés
There is a neural matrix controlling the sleep-wake cycle (SWC) embedded within high ranking integrative mechanisms in the central nervous system. Nicotinic alpha-9 acetylcholine receptor subunit (alpha-9 nAChR) participate in physiological processes occurring in sensory, endocrine and immune systems. There is a relationship between the SWC architecture, body homeostasis and sensory afferents so that disruption of afferent signaling is expected to affect the temporal organization of sleep and wake states. The analysis of the SWC of 9 nAChR knock-out animals may help to reveal the contribution of alpha-9 nAChR to sleep chronobiological determinants...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29024766/protective-effect-of-an-alpha-7-nicotinic-acetylcholine-receptor-agonist-against-enterovirus-71-infection-in-neuronal-cells
#19
Feng Xia Song, Lin Qing Zhao, Ru Nan Zhu, Qin Wei Song, Jie Deng, Run Tian, Fang Wang, Yuan Qian
Enterovirus 71, as one of the dominant pathogens associated with severe hand, foot, and mouth disease, has been well reported to trigger severe neurological symptoms among young children over the last decade, particularly among children in the Asia-Pacific region. To date, no effective antiviral agent has been developed for the treatment of severe enterovirus 71 infection. PNU-282987, a selective alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist, has been reported to have a neuroprotective effect by participating in inflammatory regulation in previous studies...
January 2018: Antiviral Research
https://www.readbyqxmd.com/read/28974241/recombinant-newcastle-disease-virus-rl-rvg-enhances-the-apoptosis-and-inhibits-the-migration-of-a549-lung-adenocarcinoma-cells-via-regulating-alpha-7-nicotinic-acetylcholine-receptors-in-vitro
#20
Yulan Yan, Chunxiang Su, Min Hang, Hua Huang, Yinghai Zhao, Xiaomei Shao, Xuefeng Bu
BACKGROUND: The aim of this study were to investigate the possible pro-apoptotic mechanisms of the recombinant Newcastle disease virus (NDV) strain rL-RVG, which expresses the rabies virus glycoprotein, in A549 lung adenocarcinoma cells via the regulation of alpha 7 nicotinic acetylcholine receptors (α7 nAChRs) and to analyze the relationships between α7 nAChR expression in lung cancer and the clinical pathological features. METHODS: α7 nAChR expression in A549, LΑ795, and small-cell lung carcinoma (SCLC) cells, among others, was detected using reverse transcription polymerase chain reaction (RT-PCR)...
October 3, 2017: Virology Journal
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