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Neuregulin-1

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https://www.readbyqxmd.com/read/28094814/meta-analysis-reveals-associations-between-genetic-variation-in-the-5-and-3-regions-of-neuregulin-1-and-schizophrenia
#1
M S Mostaid, S G Mancuso, C Liu, S Sundram, C Pantelis, I P Everall, C A Bousman
Genetic, post-mortem and neuroimaging studies repeatedly implicate neuregulin-1 (NRG1) as a critical component in the pathophysiology of schizophrenia. Although a number of risk haplotypes along with several genetic polymorphisms in the 5' and 3' regions of NRG1 have been linked with schizophrenia, results have been mixed. To reconcile these conflicting findings, we conducted a meta-analysis examining 22 polymorphisms and two haplotypes in NRG1 among 16 720 cases, 20 449 controls and 2157 family trios. We found significant associations for three polymorphisms (rs62510682, rs35753505 and 478B14-848) at the 5'-end and two (rs2954041 and rs10503929) near the 3'-end of NRG1...
January 17, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28089851/neuregulin-1-mutant-mice-indicate-motor-and-sensory-deficits-indeed-few-references-for-schizophrenia-endophenotype-model
#2
Silvia Schneider, Katja Götz, Carmen Birchmeier, Herbert Schwegler, Thomas Roskoden
Neuregulins (Nrg) are a gene family that binds to tyrosine kinase receptors of the ErbB family. The protein of Nrg1 is to be involved in heart formation, migration of neurons, axonal pathfinding and synaptic function. A relation between Nrg1 and schizophrenia is assumed. Chronic impairment in schizophrenia is characterized by different positive and negative symptoms. Detectable markers of this disease in human and in animal models are activity, social behavior and sensory processing. In this study we compared heterozygous Nrg1 mutant mice in behavior and quantification of dopaminergic and serotoninergic neurons with wild type-like littermates...
January 13, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28079007/novel-therapies-targeting-cardioprotection-and-regeneration
#3
Valeria Garrido, Evelyn Mendoza-Torres, Jaime A Riquelme, Ariel Díaz, Marcela Pizarro, Mario Bustamante, Myra N Chavez, María Paz Ocaranza, Rosemarie Mellado, Ramon Corbalan, Miguel L Allende, Sergio Lavandero
Cardiovascular disease is the leading cause of death worldwide. The heart is susceptible to pathologies that impact the myocardium directly, such myocardial infarction and consequent heart failure, as well as conditions with indirect cardiac effects, such cancer treatment-related cardiotoxicity. As the contractile cells of the heart, cardiomyocytes are essential for normal cardiac function. Various stress stimuli may result in transient damage or cell death in cardiomyocytes through apoptosis, necrosis or maladaptive autophagy...
January 12, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28065942/neuregulin-1-erbb-module-in-c-bouton-synapses-on-somatic-motor-neurons-molecular-compartmentation-and-response-to-peripheral-nerve-injury
#4
Anna Casanovas, Sara Salvany, Víctor Lahoz, Olga Tarabal, Lídia Piedrafita, Raimundo Sabater, Sara Hernández, Jordi Calderó, Josep E Esquerda
The electric activity of lower motor neurons (MNs) appears to play a role in determining cell-vulnerability in MN diseases. MN excitability is modulated by cholinergic inputs through C-type synaptic boutons, which display an endoplasmic reticulum-related subsurface cistern (SSC) adjacent to the postsynaptic membrane. Besides cholinergic molecules, a constellation of proteins involved in different signal-transduction pathways are clustered at C-type synaptic sites (M2 muscarinic receptors, Kv2.1 potassium channels, Ca(2+) activated K(+) [SK] channels, and sigma-1 receptors [S1R]), but their collective functional significance so far remains unknown...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28059646/irreversible-changes-occurring-in-long-term-denervated-schwann-cells-affect-delayed-nerve-repair
#5
Giulia Ronchi, Michele Cillino, Giovanna Gambarotta, Benedetta Elena Fornasari, Stefania Raimondo, Pierfrancesco Pugliese, Pierluigi Tos, Adriana Cordova, Francesco Moschella, Stefano Geuna
OBJECTIVE Multiple factors may affect functional recovery after peripheral nerve injury, among them the lesion site and the interval between the injury and the surgical repair. When the nerve segment distal to the lesion site undergoes chronic degeneration, the ensuing regeneration (when allowed) is often poor. The aims of the current study were as follows: 1) to examine the expression changes of the neuregulin 1/ErbB system during long-term nerve degeneration; and 2) to investigate whether a chronically denervated distal nerve stump can sustain nerve regeneration of freshly axotomized axons...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28049763/the-receptor-tyrosine-kinase-axl-mediates-nuclear-translocation-of-the-epidermal-growth-factor-receptor
#6
Toni M Brand, Mari Iida, Kelsey L Corrigan, Cara M Braverman, John P Coan, Bailey G Flanigan, Andrew P Stein, Ravi Salgia, Jana Rolff, Randall J Kimple, Deric L Wheeler
The epidermal growth factor receptor (EGFR) is a therapeutic target in patients with various cancers. Unfortunately, resistance to EGFR-targeted therapeutics is common. Previous studies identified two mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Nuclear translocation of EGFR bypasses the inhibitory effects of cetuximab, and the receptor tyrosine kinase AXL mediates cetuximab resistance by maintaining EGFR activation and downstream signaling. Thus, we hypothesized that AXL mediated the nuclear translocation of EGFR in the setting of cetuximab resistance...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/27993557/inhibition-of-endoplasmic-reticulum-stress-by-neuregulin-1-protects-against-myocardial-ischemia-reperfusion-injury
#7
Shan-Juan Fang, Peng-Yang Li, Chun-Mei Wang, Yi Xin, Wei-Wei Lu, Xiao-Xia Zhang, Song Zuo, Chang-Sheng Ma, Chao-Shu Tang, Shao-Ping Nie, Yong-Fen Qi
Neuregulin-1 (NRG-1), an endogenously produced polypeptide, is the ligand of cardiomyocyte ErbB receptors, with cardiovascular protective effects. In the present study, we explored whether the cardioprotective effect of NRG-1 against I/R injury is mediated by inhibiting myocardial endoplasmic reticulum (ER) stress. In vitro, NRG-1 directly inhibited the upregulation of ER stress markers such as glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein and cleaved caspase-12 induced by the ER stress inducers tunicamycin or dithiothreitol in both neonatal and adult ventricular myocytes...
December 16, 2016: Peptides
https://www.readbyqxmd.com/read/27988307/interleukin-6-and-neuregulin-1-as-regulators-of-utrophin-expression-via-the-activation-of-nrg-1-erbb-signaling-pathway-in-mdx-cells
#8
Nevenka Juretić, Josefina Díaz, Felipe Romero, Gustavo González, Enrique Jaimovich, Nora Riveros
Duchenne muscular dystrophy (DMD) is a neuromuscular disease originated by mutations in the dystrophin gene. A promising therapeutic approach deals with functional substitution of dystrophin by utrophin, a structural homolog that might be able to compensate dystrophin absence in DMD muscle fibers. It has been described that both interleukin-6 (IL-6) and neuregulin-1 (NRG-1; Heregulin-HRG) induce utrophin expression in skeletal muscle. We investigated a possible functional link among IL-6, NRG-1 and utrophin, in normal (C57) and dystrophic (mdx) skeletal muscle cells...
December 15, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27928246/%C3%A2-association-between-neuregulin-1-gene-variant-%C3%A2-%C3%A2-rs2439272-and-schizophrenia-and-its-negative-%C3%A2-symptoms-in-an-iranian-population
#9
Sadegh Yoosefee, Esmaeil Shahsavand Ananloo, Mohammad-Taghi Joghataei, Morteza Karimipour, Mahmoudreza Hadjighassem, Hoorie Mohaghghegh, Mehdi Tehrani-Doost, Amir-Abbas Rahimi, Hamid Mostafavi Abdolmaleky, Maryam Hatami
Objective: Although the etiology of schizophrenia is unknown, it has a significant genetic component. ‎A number of studies have indicated that neuregulin-1 (NRG1) gene may play a role in the ‎pathogenesis of schizophrenia. In this study, we examined whether the rs2439272 of NRG1 ‎is associated with schizophrenia and its negative symptoms in an Iranian population.‎ Method: Rs2439272 was genotyped in 469 participants including 276 unrelated patients with schizophrenia and 193 healthy controls. The association of genetic risk with negative ‎symptoms (by using panss) was examined in the total, male and female samples...
July 2016: Iranian Journal of Psychiatry
https://www.readbyqxmd.com/read/27918433/protein-phosphatase-1-regulates-expression-of-neuregulin-1
#10
Tatiana Ammosova, Kareem Washington, Jamie Rotimi, Namita Kumari, Kahli A Smith, Xiaomei Niu, Marina Jerebtsova, Sergei Nekhai
Protein phosphatase 1 (PP1), a cellular serine/threonine phosphatase, is targeted to cellular promoters by its major regulatory subunits, PP1 nuclear targeting subunit, nuclear inhibitor of PP1 (NIPP1) and RepoMan. PP1 is also targeted to RNA polymerase II (RNAPII) by NIPP1 where it can dephosphorylate RNAPII and cycle-dependent kinase 9 (CDK9). Here, we show that treatment of cells with a small molecule activator of PP1 increases the abundance of a neuregulin-1 (NRG-1)-derived peptide. NRG-1 mRNA and protein levels were increased in the cells stably or transiently expressing mutant NIPP1 (mNIPP1) that does not bind PP1, but not in the cells expressing NIPP1...
December 2, 2016: Biology
https://www.readbyqxmd.com/read/27916686/altered-cytokine-profile-pain-sensitivity-and-stress-responsivity-in-mice-with-co-disruption-of-the-developmental-genes-neuregulin-1%C3%A3-disc1
#11
Lieve Desbonnet, Rachel Cox, Orna Tighe, Donna Lai, Richard P Harvey, John L Waddington, Colm M P O'Tuathaigh
The complex genetic origins of many human disorders suggest that epistatic (gene×gene) interactions may contribute to a significant proportion of their heritability estimates and phenotypic heterogeneity. Simultaneous disruption of the developmental genes and schizophrenia risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) in mice has been shown to produce disease-relevant and domain-specific phenotypic profiles different from that observed following disruption of either gene alone. In the current study, anxiety and stress responsivity phenotypes in male and female mutant mice with simultaneous disruption of DISC1 and NRG1 were examined...
December 1, 2016: Behavioural Brain Research
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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