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Neuregulin

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https://www.readbyqxmd.com/read/28646138/uniting-the-neuro-developmental-and-immunological-hypotheses-neuregulin-1-receptor-erbb-and-toll-like-receptor-activation-in-first-episode-schizophrenia
#1
Szabolcs Kéri, Csilla Szabó, Oguz Kelemen
Current pathophysiological models of schizophrenia focus on neurodevelopmental and immunological mechanisms. We investigated a molecular pathway traditionally linked to the neurodevelopmental hypothesis (neuregulin 1 - ErbB), and pathogen-associated pattern recognition receptors associated with the immune hypothesis (Toll-like receptors, TLRs). We recruited 42 first-episode, drug-naïve patients with schizophrenia and 42 matched healthy control subjects. In monocytes TLR4/TLR5 and ErbB expressions were measured with flow-cytometry...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638929/-research-progress-of-neuregulin-4-biological-function
#2
Fan Yang, Xiao-Nan Li
Neuregulin 4 (NRG4) is a kind of protein containing epidermal growth factor (EGF)-like domains, mainly expressed and secreted by brown adipocytes. It specifically activates EGF receptor ErbB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) to stimulate cell proliferation, inhibit apoptosis and improve energy metabolism of cells. Increasing evidence has shown that NRG4 plays an important role in epithelial cell-related diseases, cardiovascular diseases, tumors and glycolipid metabolic diseases, and therefore it could be a potential therapeutic target of some diseases...
June 25, 2017: Sheng Li Xue Bao: [Acta Physiologica Sinica]
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#3
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28623147/neuregulin-1-protects-mouse-cerebellum-against-oxidative-stress-and-neuroinflammation
#4
Junping Xu, Chengliang Hu, Shuangxi Chen, Huifan Shen, Qiong Jiang, Peizhi Huang, Weijiang Zhao
Cerebellum undergoes degenerative changes in neurodegenerative diseases. Two main factors including oxidative stress and neuroinflammation mediate neurodegeneration. Neuregulin-1 (Nrg1) has been implicated in many neurodegenerative diseases, while the underlying mechanisms are unknown. We hypothesized that Nrg1 prevents oxidative stress and neuroinflammation in neurodegeneration. We found a positive correlation between Nrg1 protein levels and ErbB4 and ErbB2 receptor phosphorylation in microarrays of normal human cerebellar tissue...
June 13, 2017: Brain Research
https://www.readbyqxmd.com/read/28621415/building-functional-units-of-movement-generation-and-movement-sensation-in-the-embryo
#5
Peleg Hasson, Talila Volk, Adi Salzberg
The musculoskeletal and proprioceptive sensory systems exhibit intricate crosstalk between force generation, force sensation and force transmission, all of which are critical for coordinated animal locomotion. Recent developmental studies of the musculoskeletal and proprioceptive units of the invertebrate Drosophila embryo, have revealed several common molecular and structural principles mediating the formation of each of these systems. These common principles, as well as the differences between the developmental programs of the two systems, are discussed...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#6
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28608461/epidermal-growth-factor-signals-attenuate-phenotypic-and-functional-development-of-neocortical-gaba-neurons
#7
Hisaaki Namba, Tadasato Nagano, Eiichi Jodo, Satoshi Eifuku, Masao Horie, Hirohide Takebayashi, Yuriko Iwakura, Hidekazu Sotoyama, Nobuyuki Takei, Hiroyuki Nawa
Phenotypic development of neocortical GABA neurons is highly plastic and promoted by various neurotrophic factors such as neuregulin-1. A subpopulation of GABA neurons expresses not only neuregulin receptor (ErbB4) but also epidermal growth factor (EGF) receptor (ErbB1) during development, but the neurobiological action of EGF on this cell population is less understood than that of neuregulin-1. Here we examined the effects of exogenous EGF on immature GABA neurons both in culture and in vivo and also explored physiological consequences in adults...
June 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28592819/spatial-and-temporal-boundaries-of-nmda-receptor-hypofunction-leading-to-schizophrenia
#8
Kazu Nakazawa, Vivek Jeevakumar, Kazuhito Nakao
The N-methyl-D-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-D-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-D-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-D-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially...
February 3, 2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28582279/prevalence-and-influence-on-outcome-of-her2-neu-her3-and-nrg1-expression-in-patients-with-metastatic-colorectal-cancer
#9
Arndt Stahler, Volker Heinemann, Jens Neumann, Alexander Crispin, Andreas Schalhorn, Sebastian Stintzing, Clemens Giessen-Jung, Ludwig Fischer von Weikersthal, Ursula Vehling-Kaiser, Martina Stauch, Detlef Quietzsch, Julian W Holch, Stephan Kruger, Michael Haas, Marlies Michl, Jobst von Einem, Thomas Kirchner, Andreas Jung, Dominik P Modest
Our aim was to explore the impact of the HER2/neu, HER3 receptor as well as their ligands' neuregulin (NRG1) expression on the outcome of patients with metastatic colorectal cancer (mCRC). NRG1, HER2/neu and HER3 expression was evaluated in 208 patients with mCRC receiving 5-FU/LV plus irinotecan or irinotecan plus oxaliplatin as the first-line treatment. Biomarker expression was correlated with the outcome of patients. NRG1 (low: 192 vs. high: 16), HER2/neu (low: 201 vs. high: 7) and HER3 (low: 69 vs. high: 139) expressions were assessed in 208 patients...
June 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28577921/parent-of-origin-effects-on-schizophrenia-relevant-behaviours-of-type-iii-neuregulin-1-mutant-mice
#10
Kani Shang, David A Talmage, Tim Karl
A robust, disease-relevant phenotype is paramount to the validity of genetic mouse models, which are an important tool in understanding complex diseases. Recent evidence from genome-wide association studies suggests the genetic contribution of parents to offspring is not equivalent. Despite this, few studies to date have examined the potential impact of parent genotype (i.e. origin of mutation) on the offspring of disease-relevant genetic mouse models. To elucidate the potential impact of the sex of the mutant parent on offspring phenotype, we characterized male and female offspring of an established schizophrenia mouse model, which had been generated using two different breeding schemes, in a range of disease-relevant behaviours...
May 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28573357/clinical-significance-of-overexpression-of-nrg1-and-its-receptors-her3-and-her4-in-gastric-cancer-patients
#11
Sumi Yun, Jiwon Koh, Soo Kyung Nam, Jung Ok Park, Sung Mi Lee, Kyoungyul Lee, Kyu Sang Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Gheeyoung Choe, Woo Ho Kim, Hye Seung Lee
BACKGROUND: Neuregulin 1 (NRG1), a ligand for human epidermal growth factor (HER) 3 and HER4, can activates cell signaling pathways to promote carcinogenesis and metastasis. METHODS: To investigate the clinicopathologic significance of NRG1 and its receptors, immunohistochemistry was performed for NRG1, HER3, and HER4 in 502 consecutive gastric cancers (GCs). Furthermore, HER2, microsatellite instability (MSI), and Epstein-Barr virus (EBV) status were investigated...
June 1, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28560253/spatial-and-temporal-boundaries-of-nmda-receptor-hypofunction-leading-to-schizophrenia
#12
Kazu Nakazawa, Vivek Jeevakumar, Kazuhito Nakao
The N-methyl-d-aspartate receptor hypofunction is one of the most prevalent models of schizophrenia. For example, healthy subjects treated with uncompetitive N-methyl-d-aspartate receptor antagonists elicit positive, negative, and cognitive-like symptoms of schizophrenia. Patients with anti-N-methyl-d-aspartate receptor encephalitis, which is likely caused by autoantibody-mediated down-regulation of cell surface N-methyl-d-aspartate receptors, often experience psychiatric symptoms similar to schizophrenia initially...
2017: NPJ Schizophrenia
https://www.readbyqxmd.com/read/28556469/neuregulin-3-and-its-roles-in-schizophrenia-risk-and-presentation
#13
REVIEW
Dimitrios Avramopoulos
Neuregulins, a four-member family of epidermal growth factor-like signaling molecules, have been studied for over two decades. They were first implicated in schizophrenia in 2002 with the detection of linkage and association at the NRG1 locus followed after a few years by NRG3. However, the associations with disease have not been very consistently observed. In contrast, association of NGR3 variants with disease presentation, specifically the presence of delusions, has been more consistent. This appears to be mediated by quantitative changes in the alternative splicing of the gene, which has also been consistently observed...
May 29, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28542067/grb2-associated-binder-1-is-required-for-extrafusal-and-intrafusal-muscle-fiber-development
#14
So Y Park, So Y Jang, Yoon K Shin, Byeol A Yoon, Hye J Lee, Hwan T Park
The neuregulin-1 (NRG1) signaling pathway plays an important role in the development of the peripheral neuromuscular system, including in muscle spindle and postnatal myelination. We previously showed that NRG1 on the axonal membrane regulates peripheral nerve myelination through Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling. Here, we determined the role of Gab1 in the development of muscles and the muscle spindle using muscle-specific conditional Gab1 knockout mice...
July 5, 2017: Neuroreport
https://www.readbyqxmd.com/read/28507002/neuregulin-1-allosterically-enhances-the-antitumor-effects-of-the-noncompeting-anti-her3-antibody-9f7-f11-by-increasing-its-binding-to-her3
#15
Christophe Le Clorennec, Hervé Bazin, Olivier Dubreuil, Christel Larbouret, Charline Ogier, Yassamine Lazrek, Véronique Garambois, Marie-Alix Poul, Philippe Mondon, Jean-Marc Barret, Gérard Mathis, Jean-François Prost, André Pèlegrin, Thierry Chardès
Exploratory clinical trials using therapeutic anti-HER3 antibodies strongly suggest that neuregulin (NRG1; HER3 ligand) expression at tumor sites is a predictive biomarker of anti-HER3 antibody efficacy in cancer. We hypothesized that in NRG1-expressing tumors, where the ligand is present before antibody treatment, anti-HER3 antibodies that do not compete with NRG1 for receptor binding have a higher receptor-neutralizing action than antibodies competing with the ligand for binding to HER3. Using time-resolved-fluorescence energy transfer (TR-FRET), we demonstrated that in the presence of recombinant NRG1, binding of 9F7-F11 (a nonligand-competing anti-HER3 antibody) to HER3 is increased, whereas that of ligand-competing anti-HER3 antibodies (H4B-121, U3-1287, Ab#6, Mab205...
May 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28506533/schwann-cell-precursors-from-human-pluripotent-stem-cells-as-a-potential-therapeutic-target-for-myelin-repair
#16
Han-Seop Kim, Jungwoon Lee, Da Yong Lee, Young-Dae Kim, Jae Yun Kim, Hyung Jin Lim, Sungmin Lim, Yee Sook Cho
Schwann cells play a crucial role in successful nerve repair and regeneration by supporting both axonal growth and myelination. However, the sources of human Schwann cells are limited both for studies of Schwann cell development and biology and for the development of treatments for Schwann cell-associated diseases. Here, we provide a rapid and scalable method to produce self-renewing Schwann cell precursors (SCPs) from human pluripotent stem cells (hPSCs), using combined sequential treatment with inhibitors of the TGF-β and GSK-3 signaling pathways, and with neuregulin-1 for 18 days under chemically defined conditions...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28497176/five-weekly-s-1-plus-cisplatin-therapy-combined-with-trastuzumab-therapy-in-her2-positive-gastric-cancer-a-phase-ii-trial-and-biomarker-study-wjog7212g
#17
Yuji Miura, Yasutaka Sukawa, Shuichi Hironaka, Misuzu Mori, Kazuhiro Nishikawa, Shinya Tokunaga, Hiroyuki Okuda, Takeshi Sakamoto, Keisei Taku, Kazuo Nishikawa, Toshikazu Moriwaki, Yuji Negoro, Yutaka Kimura, Keita Uchino, Katsunori Shinozaki, Hiroharu Shinozaki, Nobuyuki Musha, Hirotsugu Yoshiyama, Takashi Tsuda, Yoshinori Miyata, Naotoshi Sugimoto, Tsuyoshi Shirakawa, Miki Ito, Kimio Yonesaka, Kenichi Yoshimura, Narikazu Boku, Katsuhiko Nosho, Toshimi Takano, Ichinosuke Hyodo
BACKGROUND: Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear. METHODS: Patients received 5-weekly SP therapy (S-1 at 40-60 mg twice daily for 21 days plus cisplatin at 60 mg/m(2) on day 8, every 5 weeks) plus trastuzumab therapy (first dose of 8 mg/kg, then 6 mg/kg every 3 weeks)...
May 11, 2017: Gastric Cancer
https://www.readbyqxmd.com/read/28496106/neuregulin-1-improves-complex-2-mediated-mitochondrial-respiration-in-skeletal-muscle-of-healthy-and-diabetic-mice
#18
Gaël Ennequin, Frederic Capel, Kevin Caillaud, Vivien Chavanelle, Monique Etienne, Allison Teixeira, Xinyan Li, Nathalie Boisseau, Pascal Sirvent
It has been reported that neuregulin1 (NRG1) improves glucose tolerance in healthy and diabetic rodents. In vitro studies also suggest that NRG1 regulates myocyte oxidative capacity. To confirm this observation in vivo, we evaluated the effect on mitochondrial function of an 8-week treatment with NRG1 in db/db diabetic mice and C57BL/6JRJ healthy controls. NRG1 treatment improved complex 2-mediated mitochondrial respiration in the gastrocnemius of both control and diabetic mice and increased mitochondrial complex 2 subunit content by 2-fold...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28485381/regulation-of-cardiomyocyte-behavior-in-zebrafish-trabeculation-by-neuregulin-2a-signaling
#19
S Javad Rasouli, Didier Y R Stainier
Trabeculation is crucial for cardiac muscle growth in vertebrates. This process requires the Erbb2/4 ligand Neuregulin (Nrg), secreted by the endocardium, as well as blood flow/cardiac contractility. Here, we address two fundamental, yet unresolved, questions about cardiac trabeculation: why does it initially occur in the ventricle and not the atrium, and how is it modulated by blood flow/contractility. Using loss-of-function approaches, we first show that zebrafish Nrg2a is required for trabeculation, and using a protein-trap line, find that it is expressed in both cardiac chambers albeit with different spatiotemporal patterns...
May 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28472537/phase-1-2-study-of-rilotumumab-amg-102-a-hepatocyte-growth-factor-inhibitor-and-erlotinib-in-patients-with-advanced-non-small-cell-lung-cancer
#20
Ahmad A Tarhini, Imran Rafique, Theofanis Floros, Phu Tran, William E Gooding, Liza C Villaruz, Timothy F Burns, David M Friedland, Daniel P Petro, Mariya Farooqui, Jose Gomez-Garcia, Autumn Gaither-Davis, Sanja Dacic, Athanassios Argiris, Mark A Socinski, Laura P Stabile, Jill M Siegfried
BACKGROUND: Activation of the mesenchymal-epidermal transition factor (MET) tyrosine kinase and its ligand, hepatocyte growth factor (HGF), is implicated in resistance to epidermal growth factor receptor (EGFR) inhibitors. In this phase 1/2 trial, rilotumumab (an anti-HGF antibody) combined with erlotinib was evaluated in patients with metastatic, previously treated non-small cell lung cancer. METHODS: In phase 1, a dose de-escalation design was adopted with rilotumumab starting at 15 mg/kg intravenously every 3 weeks and oral erlotinib 150 mg daily...
May 4, 2017: Cancer
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