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Neuregulin-1

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https://www.readbyqxmd.com/read/27913953/neuroinflammation-induced-downregulation-of-hippocampacal-neuregulin-1-erbb4-signaling-in-the-parvalbumin-interneurons-might-contribute-to-cognitive-impairment-in-a-mouse-model-of-sepsis-associated-encephalopathy
#1
Rong Gao, Mu-Huo Ji, Da-Peng Gao, Run-Hua Yang, Shao-Gang Zhang, Jian-Jun Yang, Jin-Chun Shen
Sepsis-associated encephalopathy (SAE) is a common complication associated with poor prognosis in septic patients, but the underlying mechanism remains unclear. We hypothesized that disturbed neuregulin 1 (NRG1)-ErbB4 signaling in the parvalbumin interneurons was involved in sepsis-induced cognitive impairment in a mouse model of SAE. The SAE model was induced by cecal ligation/perforation (CLP). Animals were randomly divided into the following six groups: sham + vehicle group, sham + NRG1 group, CLP + vehicle group, CLP + NRG1 group, CLP + NRG1 + AG1478 (ErbB4 inhibitor) group, and CLP + minocycline group...
December 2, 2016: Inflammation
https://www.readbyqxmd.com/read/27882385/a-role-for-neuregulin-1-in-promoting-keloid-fibroblast-migration-via-erbb2-mediated-signaling
#2
Natalie Jumper, Tom Hodgkinson, Ralf Paus, Ardeshir Bayat
Keloid disease is a fibroproliferative tumour characterised by aggressive local invasion, evident from a clinically and histologically active migrating margin. During combined laser capture microdissection and microarray analysis-based in situ gene expression profiling, we identified upregulation of the polypeptide growth factor neuregulin-1 (NRG1) and ErbB2 oncogene in keloid margin dermis, leading to the hypothesis that NRG1 contributed to keloid margin migration through ErbB2-mediated signalling. The aim of this study was to probe this hypothesis through functional in vitro studies...
November 24, 2016: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/27876763/growth-factor-and-co-receptor-release-by-structural-regulation-of-substrate-metalloprotease-accessibility
#3
Liseth M Parra, Monika Hartmann, Salome Schubach, Junzhi Ma, Peter Herrlich, Andreas Herrlich
Release of cytokines, growth factors and other life-essential molecules from precursors by a-disintegrin-and-metalloproteases (ADAMs) is regulated with high substrate-specificity. We hypothesized that this is achieved by cleavage-regulatory intracellular-domain (ICD)-modifications of the precursors. We show here that cleavage-stimuli-induced specific ICD-modifications cause structural substrate changes that enhance ectodomain sensitivity of neuregulin-1 (NRG1; epidermal-growth-factor) or CD44 (receptor-tyrosine-kinase (RTK) co-receptor) to chymotrypsin/trypsin or soluble ADAM...
November 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27861634/molecular-characterization-of-striated-muscle-specific-gab1-isoform-as-a-critical-signal-transducer-for-neuregulin-1-erbb-signaling-in-cardiomyocytes
#4
Taku Yasui, Takeshi Masaki, Yoh Arita, Tomohiko Ishibashi, Tadakatsu Inagaki, Makoto Okazawa, Toru Oka, Wataru Shioyama, Keiko Yamauchi-Takihara, Issei Komuro, Yasushi Sakata, Yoshikazu Nakaoka
Grb2-associated binder (Gab) docking proteins regulate signals downstream of a variety of growth factors and receptor tyrosine kinases. Neuregulin-1 (NRG-1), a member of epidermal growth factor family, plays a critical role for cardiomyocyte proliferation and prevention of heart failure via ErbB receptors. We previously reported that Gab1 and Gab2 in the myocardium are essential for maintenance of myocardial function in the postnatal heart via transmission of NRG-1/ErbB-signaling through analysis of Gab1/Gab2 cardiomyocyte-specific double knockout mice...
2016: PloS One
https://www.readbyqxmd.com/read/27847649/neuregulin-1-regulates-cortical-inhibitory-neuron-dendrite-and-synapse-growth-through-disc1
#5
Brianna K Unda, Vickie Kwan, Karun K Singh
Cortical inhibitory neurons play crucial roles in regulating excitatory synaptic networks and cognitive function and aberrant development of these cells have been linked to neurodevelopmental disorders. The secreted neurotrophic factor Neuregulin-1 (NRG1) and its receptor ErbB4 are established regulators of inhibitory neuron connectivity, but the developmental signalling mechanisms regulating this process remain poorly understood. Here, we provide evidence that NRG1-ErbB4 signalling functions through the multifunctional scaffold protein, Disrupted in Schizophrenia 1 (DISC1), to regulate the development of cortical inhibitory interneuron dendrite and synaptic growth...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27846271/igg-containing-isoforms-of-neuregulin-1-are-dispensable-for-cardiac-trabeculation-in-zebrafish
#6
Leigh Ann Samsa, Cade Ellis Ito, Daniel Ross Brown, Li Qian, Jiandong Liu
The Neuregulin-1 (Nrg1) signaling pathway has been widely implicated in many aspects of heart development including cardiac trabeculation. Cardiac trabeculation is an important morphogenetic process where clusters of ventricular cardiomyocytes extrude and expand into the lumen of the ventricular chambers. In mouse, Nrg1 isoforms containing an immunoglobulin-like (IgG) domain are essential for cardiac trabeculation through interaction with heterodimers of the epidermal growth factor-like (EGF-like) receptors ErbB2/ErbB4...
2016: PloS One
https://www.readbyqxmd.com/read/27845301/effects-of-epinephrine-on-angiogenesis-related-gene-expressions-in-cultured-rat-cardiomyocytes
#7
Henry Liu, Lisa Sangkum, Geoffrey Liu, Michael Green, Marilyn Li, Alan Kaye
Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression of angiopoietin-2 gene (+2...
September 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27843803/randomized-phase-ii-study-of-duligotuzumab-mehd7945a-vs-cetuximab-in-squamous-cell-carcinoma-of-the-head-and-neck-mehgan-study
#8
Jérôme Fayette, Lori Wirth, Cristina Oprean, Anghel Udrea, Antonio Jimeno, Danny Rischin, Christopher Nutting, Paul M Harari, Tibor Csoszi, Dana Cernea, Paul O'Brien, William D Hanley, Amy V Kapp, Maria Anderson, Elicia Penuel, Bruce McCall, Andrea Pirzkall, Jan B Vermorken
BACKGROUND: Duligotuzumab, a novel dual-action humanized IgG1 antibody that blocks ligand binding to epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 3 (HER3), inhibits signaling from all ligand-dependent HER dimers, and can elicit antibody-dependent cell-mediated cytotoxicity. High tumor-expression of neuregulin 1 (NRG1), a ligand to HER3, may enhance sensitivity to duligotuzumab. METHODS: This multicenter, open-label, randomized phase II study (MEHGAN) evaluated drug efficacy in patients with recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) progressive on/after chemotherapy and among patients with NRG1-high tumors...
2016: Frontiers in Oncology
https://www.readbyqxmd.com/read/27824163/the-role-of-p2x7-receptors-in-a-rodent-pcp-induced-schizophrenia-model
#9
Bence Koványi, Cecilia Csölle, Stefano Calovi, Adrienn Hanuska, Erzsébet Kató, László Köles, Anindya Bhattacharya, József Haller, Beáta Sperlágh
P2X7 receptors (P2X7Rs) are ligand-gated ion channels sensitive to extracellular ATP. Here we examined for the first time the role of P2X7R in an animal model of schizophrenia. Using the PCP induced schizophrenia model we show that both genetic deletion and pharmacological inhibition of P2X7Rs alleviate schizophrenia-like behavioral alterations. In P2rx7+/+ mice, PCP induced hyperlocomotion, stereotype behavior, ataxia and social withdrawal. In P2X7 receptor deficient mice (P2rx7-/-), the social interactions were increased, whereas the PCP induced hyperlocomotion and stereotype behavior were alleviated...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799291/niacin-mediated-tace-activation-ameliorates-cmt-neuropathies-with-focal-hypermyelination
#10
Alessandra Bolino, Françoise Piguet, Valeria Alberizzi, Marta Pellegatta, Cristina Rivellini, Marta Guerrero-Valero, Roberta Noseda, Chiara Brombin, Alessandro Nonis, Patrizia D'Adamo, Carla Taveggia, Stefano Carlo Previtali
Charcot-Marie-Tooth (CMT) neuropathies are highly heterogeneous disorders caused by mutations in more than 70 genes, with no available treatment. Thus, it is difficult to envisage a single suitable treatment for all pathogenetic mechanisms. Axonal Neuregulin 1 (Nrg1) type III drives Schwann cell myelination and determines myelin thickness by ErbB2/B3-PI3K-Akt signaling pathway activation. Nrg1 type III is inhibited by the α-secretase Tace, which negatively regulates PNS myelination. We hypothesized that modulation of Nrg1 levels and/or secretase activity may constitute a unifying treatment strategy for CMT neuropathies with focal hypermyelination as it could restore normal levels of myelination...
December 1, 2016: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27784625/nicotine-induced-neuroplasticity-counteracts-the-effect-of-schizophrenia-linked-neuregulin-1-signaling-on-nmdar-function-in-the-rat-hippocampus
#11
Yoshihiko Yamazaki, Katumi Sumikawa
A high rate of heavy tobacco smoking among people with schizophrenia has been suggested to reflect self-medication and amelioration of cognitive dysfunction, a core feature of schizophrenia. NMDAR hypofunction is hypothesized to be a mechanism of cognitive dysfunction, and excessive schizophrenia-linked neuregulin 1 (NRG1) signaling through its receptor ErbB4 can suppress NMDAR function by preventing Src-mediated enhancement of NMDAR responses. Here we investigated whether chronic nicotine exposure in rats by subcutaneous injection of nicotine (0...
October 23, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27777309/her4-suppresses-p53-via-targeting-the-mdmx-mdm2-complex-implication-of-a-novel-mdmx-ser314-phosphosite
#12
Casimiro Gerarduzzi, Anna de Polo, Xue-Song Liu, Manale El Kharbili, John B Little, Zhi-Min Yuan
Deregulated receptor tyrosine kinase (RTK) signaling is frequently associated with tumorigenesis and therapy resistance, but its underlying mechanisms still need to be elucidated. In this study we have shown that the RTK human epidermal growth factor receptor 4 (Her4, aka Erbb4) can inhibit the tumor suppressor p53 by regulating the MDMX-MDM2 complex stabilization. Upon activation by either overexpression of a constitutively active vector or ligand binding (Neuregulin-1), Her4 was able to stabilize the MDMX-MDM2 complex resulting in suppression of p53 transcriptional activity, as shown by p53 responsive element-driven luciferase assay and mRNA levels of p53 target genes...
October 24, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27755239/pathophysiology-of-cardiotoxicity-from-target-therapy-and-angiogenesis-inhibitors
#13
Nicola Maurea, Carmela Coppola, Giovanna Piscopo, Francesca Galletta, Gennaro Riccio, Emanuela Esposito, Claudia De Lorenzo, Michelino De Laurentiis, Paolo Spallarossa, Giuseppe Mercuro
The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others...
May 2016: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/27732090/neuregulin-1-regulates-proliferation-of-leydig-cells-to-support-spermatogenesis-and-sexual-behavior-in-adult-mice
#14
Takashi Umehara, Ikko Kawashima, Tomoko Kawai, Yumi Hoshino, Ken-Ichirou Morohashi, Yuichi Shima, Wenxian Zeng, JoAnne S Richards, Masayuki Shimada
Adult Leydig cells are derived from proliferating stem/progenitor Leydig cells in the infant testis and subsequent differentiation to steroidogenic cells in adult mice. Leydig cell proliferation in the infant testis occurs primarily in response to increased levels of LH that induce Leydig cell expression of neuregulin 1 (NRG1). Depletion of NRG1 in Nrg1 mutant mice (Nrg1(flox;flox);Cyp19a1Cre mice) dramatically reduces Leydig cell proliferation in the infant testes, leading to a reduction of testis weight, epididymial weight, and serum T in the adult mutant mice...
December 2016: Endocrinology
https://www.readbyqxmd.com/read/27707970/a-ret-er81-nrg1-signaling-pathway-drives-the-development-of-pacinian-corpuscles
#15
Michael S Fleming, Jian J Li, Daniel Ramos, Tong Li, David A Talmage, Shin-Ichi Abe, Silvia Arber, Wenqin Luo
: Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET(+) mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27641496/neuregulin-1-erbb4-signaling-regulates-visual-cortical-plasticity
#16
Yanjun Sun, Taruna Ikrar, Melissa F Davis, Nian Gong, Xiaoting Zheng, Z David Luo, Cary Lai, Lin Mei, Todd C Holmes, Sunil P Gandhi, Xiangmin Xu
Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear...
October 5, 2016: Neuron
https://www.readbyqxmd.com/read/27629765/human-induced-pluripotent-cell-derived-sensory-neurons-for-fate-commitment-of-bone-marrow-derived-schwann-cells-implications-for-remyelination-therapy
#17
Sa Cai, Lei Han, Qiang Ao, Ying-Shing Chan, Daisy Kwok-Yan Shum
: : Strategies that exploit induced pluripotent stem cells (iPSCs) to derive neurons have relied on cocktails of cytokines and growth factors to bias cell-signaling events in the course of fate choice. These are often costly and inefficient, involving multiple steps. In this study, we took an alternative approach and selected 5 small-molecule inhibitors of key signaling pathways in an 8-day program to induce differentiation of human iPSCs into sensory neurons, reaching ≥80% yield in terms of marker proteins...
September 14, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27626312/oncogenic-function-and-clinical-implications-of-slc3a2-nrg1-fusion-in-invasive-mucinous-adenocarcinoma-of-the-lung
#18
Dong Hoon Shin, Donghoon Lee, Dong Wan Hong, Seung Hyun Hong, Jung-Ah Hwang, Byung Il Lee, Hye Jin You, Geon Kook Lee, In-Hoo Kim, Yeon-Su Lee, Ji-Youn Han
The neuregulin 1 (NRG1) fusion is a recently identified novel driver oncogene in invasive mucinous adenocarcinoma of the lung (IMA). After identification of a case of SLC3A2-NRG1 in a patient with IMA, we verified this fusion gene in a cohort of 59 patients with IMA. Targeted cancer panel sequencing and RT-PCR identified the possible coexistence of other driver oncogenes. Among 59 IMAs, we found 16 NRG1 fusions (13 SLC3A2-NRG1 and 3 CD74-NRG1). Of 16 patients with NRG1 fusions, concurrent KRAS codon 12 mutations were found in 10 cases...
September 8, 2016: Oncotarget
https://www.readbyqxmd.com/read/27621269/tdp-43-loss-of-function-inhibits-endosomal-trafficking-and-alters-trophic-signaling-in-neurons
#19
Benjamin M Schwenk, Hannelore Hartmann, Alperen Serdaroglu, Martin H Schludi, Daniel Hornburg, Felix Meissner, Denise Orozco, Alessio Colombo, Sabina Tahirovic, Meike Michaelsen, Franziska Schreiber, Simone Haupt, Michael Peitz, Oliver Brüstle, Clemens Küpper, Thomas Klopstock, Markus Otto, Albert C Ludolph, Thomas Arzberger, Peer-Hendrik Kuhn, Dieter Edbauer
Nuclear clearance of TDP-43 into cytoplasmic aggregates is a key driver of neurodegeneration in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but the mechanisms are unclear. Here, we show that TDP-43 knockdown specifically reduces the number and motility of RAB11-positive recycling endosomes in dendrites, while TDP-43 overexpression has the opposite effect. This is associated with delayed transferrin recycling in TDP-43-knockdown neurons and decreased β2-transferrin levels in patient CSF Whole proteome quantification identified the upregulation of the ESCRT component VPS4B upon TDP-43 knockdown in neurons...
September 12, 2016: EMBO Journal
https://www.readbyqxmd.com/read/27613806/epistatic-and-independent-effects-on-schizophrenia-related-phenotypes-following-co-disruption-of-the-risk-factors-neuregulin-1-%C3%A3-disc1
#20
Colm M P O'Tuathaigh, Fabio Fumagalli, Lieve Desbonnet, Francesc Perez-Branguli, Gerard Moloney, Samim Loftus, Claire O'Leary, Emilie Petit, Rachel Cox, Orna Tighe, Gerard Clarke, Donna Lai, Richard P Harvey, John F Cryan, Kevin J Mitchell, Timothy G Dinan, Marco A Riva, John L Waddington
Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas...
September 9, 2016: Schizophrenia Bulletin
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