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Neuregulin

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https://www.readbyqxmd.com/read/28542067/grb2-associated-binder-1-is-required-for-extrafusal-and-intrafusal-muscle-fiber-development
#1
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...
May 24, 2017: Neuroreport
https://www.readbyqxmd.com/read/28507002/neuregulin-1-allosterically-enhances-the-anti-tumor-effects-of-the-non-competing-anti-her3-antibody-9f7-f11-by-increasing-its-binding-to-her3
#2
Christophe Le Clorennec, Hervé Bazin, Olivier Dubreuil, Christel Larbouret, Charline Ogier, Yassamine Lazrek, Veronique 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 non-ligand 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
#3
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...
May 11, 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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/28456012/neuregulin-1-positively-modulates-glial-response-and-improves-neurological-recovery-following-traumatic-spinal-cord-injury
#8
Arsalan Alizadeh, Scott M Dyck, Hardeep Kataria, Ghazaleh M Shahriary, Dung H Nguyen, Kallivalappil T Santhosh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI...
April 29, 2017: Glia
https://www.readbyqxmd.com/read/28448983/intrauterine-growth-restriction-alters-the-postnatal-development-of-the-rat-cerebellum
#9
Annie R A McDougall, Vanny Wiradjaja, Aminath Azhan, Anqi Li, Nadia Hale, Mary E Wlodek, Stuart B Hooper, Megan J Wallace, Mary Tolcos
Intrauterine growth restriction (IUGR) is a major cause of antenatal brain injury. We aimed to characterize cerebellar deficits following IUGR and to investigate the potential underlying cellular and molecular mechanisms. At embryonic day 18, pregnant rats underwent either sham surgery (controls; n = 23) or bilateral uterine vessel ligation to restrict blood flow to fetuses (IUGR; n = 20). Offspring were collected at postnatal day 2 (P2), P7, and P35. Body weights were reduced at P2, P7, and P35 in IUGR offspring (p < 0...
April 28, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#10
Detlef Vullhorst, Tanveer Ahmad, Irina Karavanova, Carolyn Keating, Andres Buonanno
The Neuregulin (NRG) family of ErbB ligands is comprised of numerous variants originating from the use of different genes, alternative promoters and splice variants. NRGs have generally been thought to be transported to axons and presynaptic terminals where they signal via ErbB3/4 receptors in paracrine or juxtacrine mode. However, we recently demonstrated that unprocessed pro-NRG2 accumulates on cell bodies and proximal dendrites, and that NMDAR activity is required for shedding of its ectodomain by metalloproteinases...
April 21, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28430337/circulating-neuregulin-1-and-galectin-3-can-be-prognostic-markers-in-breast-cancer
#11
Francesca De Iuliis, Gerardo Salerno, Ludovica Taglieri, Rosina Lanza, Patrizia Cardelli, Susanna Scarpa
BACKGROUND: It is important to identify novel plasmatic biomarkers that can contribute to assessing the prognosis and outcome of breast cancer patients. Neuregulin-1 (NRG1) and galectin-3 (Gal-3) are proteins that are involved in breast cancer development and patient survival; therefore, we studied whether the serum concentration of these 2 proteins can be correlated to breast cancer progression. METHODS: Plasmatic NRG1 and Gal-3 were evaluated in 25 healthy controls and 50 breast cancer patients at baseline and at 3 and 6 months after treatment with anthracyclines and taxanes, with or without trastuzumab...
April 18, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28425448/corrigendum-visualization-of-neuregulin-1-ectodomain-shedding-reveals-its-local-processing-in-vitro-and-in-vivo
#12
Aosa Kamezaki, Fuminori Sato, Kazuhiro Aoki, Kazuhide Asakawa, Koichi Kawakami, Fumio Matsuzaki, Atsuko Sehara-Fujisawa
No abstract text is available yet for this article.
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28403399/the-role-of-microglia-in-the-pathobiology-of-neuropathic-pain-development-what-do-we-know
#13
H Zhao, A Alam, Q Chen, M A Eusman, A Pal, S Eguchi, L Wu, D Ma
Neuropathic pain, a maladaptive and chronic condition that can develop after a lesion or disease affecting the somatosensory system, is characterized by allodynia, hyperalgesia and spontaneous pain, and comorbidities such as sleep deprivation, depression and anxiety. The activation of microglial cells in response to nerve injury has been implicated in the development of neuropathic pain. Mediators such as Neuregulin-1, matrix metalloproteinase (MMP)-2, MMP-9, The chemokine (C-C motif) ligand 2 (CCL2) and fractalkine are released after nerve injury and are involved in the activation of microglial cells...
April 1, 2017: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/28396702/interaction-between-prenatal-pesticide-exposure-and-a-common-polymorphism-in-the-pon1-gene-on-dna-methylation-in-genes-associated-with-cardio-metabolic-disease-risk-an-exploratory%C3%A2-study
#14
Ken Declerck, Sylvie Remy, Christine Wohlfahrt-Veje, Katharina M Main, Guy Van Camp, Greet Schoeters, Wim Vanden Berghe, Helle R Andersen
BACKGROUND: Prenatal environmental conditions may influence disease risk in later life. We previously found a gene-environment interaction between the paraoxonase 1 (PON1) Q192R genotype and prenatal pesticide exposure leading to an adverse cardio-metabolic risk profile at school age. However, the molecular mechanisms involved have not yet been resolved. It was hypothesized that epigenetics might be involved. The aim of the present study was therefore to investigate whether DNA methylation patterns in blood cells were related to prenatal pesticide exposure level, PON1 Q192R genotype, and associated metabolic effects observed in the children...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28394697/genetic-study-of-neuregulin-1-and-receptor-tyrosine-protein-kinase-erbb-4-in-tardive-dyskinesia
#15
Clement C Zai, Arun K Tiwari, Nabilah I Chowdhury, Zeynep Yilmaz, Vincenzo de Luca, Daniel J Müller, Steven G Potkin, Jeffrey A Lieberman, Herbert Y Meltzer, Aristotle N Voineskos, Gary Remington, James L Kennedy
OBJECTIVES: Tardive dyskinesia (TD) is a movement disorder that may develop as a side effect of antipsychotic medication. The aetiology underlying TD is unclear, but a number of mechanisms have been proposed. METHODS: We investigated single-nucleotide polymorphisms (SNPs) in the genes coding for neuregulin-1 and erbB-4 receptor in our sample of 153 European schizophrenia patients for possible association with TD. RESULTS: We found the ERBB4 rs839523 CC genotype to be associated with risk for TD occurrence and increased severity as measured by the Abnormal Involuntary Movement Scale (AIMS) (P = ...
April 10, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28350885/glutamate-dependent-ectodomain-shedding-of-neuregulin-1-type-ii-precursors-in-rat-forebrain-neurons
#16
Yuriko Iwakura, Ran Wang, Naoko Inamura, Kazuaki Araki, Shigeki Higashiyama, Nobuyuki Takei, Hiroyuki Nawa
The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells...
2017: PloS One
https://www.readbyqxmd.com/read/28338897/specialized-information-processing-deficits-and-distinct-metabolomic-profiles-following-tm-domain-disruption-of-nrg1
#17
Colm M P O'Tuathaigh, Naina Mathur, Matthew J O'Callaghan, Lynsey MacIntyre, Richard Harvey, Donna Lai, John L Waddington, Benjamin S Pickard, David G Watson, Paula M Moran
Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain...
March 11, 2017: Schizophrenia Bulletin
https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#18
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
See Saporta and Shy (doi:10.1093/awx048) for a scientific commentary on this article.Effective bidirectional signalling between axons and Schwann cells is essential for both the development and maintenance of peripheral nerve function. We have established conditions by which human induced pluripotent stem cell-derived sensory neurons can be cultured with rat Schwann cells, and have produced for the first time long-term and stable myelinating co-cultures with human neurons. These cultures contain the specialized domains formed by axonal interaction with myelinating Schwann cells, such as clustered voltage-gated sodium channels at the node of Ranvier and Shaker-type potassium channel (Kv1...
April 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28322798/neuregulin-1-type-iii-knockout-mice-exhibit-delayed-migration-of-schwann-cell-precursors
#19
Yuki Miyamoto, Tomohiro Torii, Akito Tanoue, Kazuko Kawahara, Miyuki Arai, Hideki Tsumura, Toru Ogata, Motoshi Nagao, Nobuo Terada, Masahiro Yamamoto, Shou Takashima, Junji Yamauchi
In an embryonic developmental stage of the peripheral nervous system (PNS), Schwann cell precursors migrate along neuronal axons to their final destinations. After birth, they eventually wrap around individual axons to form myelin sheaths, which insulate axons to increase the nerve conduction velocity. Some growth factors and adhesion molecules are known to control these developmental stages from in the fish to in the mammal. Neuregulin-1 (NRG1), which is composed of many alternative splicing variants, is such a growth factor...
March 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28322273/neuregulin-2-ablation-results-in-dopamine-dysregulation-and-severe-behavioral-phenotypes-relevant-to-psychiatric-disorders
#20
L Yan, A Shamir, M Skirzewski, E Leiva-Salcedo, O B Kwon, I Karavanova, D Paredes, O Malkesman, K R Bailey, D Vullhorst, J N Crawley, A Buonanno
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function...
March 21, 2017: Molecular Psychiatry
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