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Neuregulin

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https://www.readbyqxmd.com/read/28432142/structural-similarities-between-neuregulin-1-3-isoforms-determine-their-subcellular-distribution-and-signaling-mode-in-central-neurons
#1
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
#2
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 14, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28320942/egf-and-nrg-induce-phosphorylation-of-her3-erbb3-by-egfr-using-distinct-oligomeric-mechanisms
#12
Bettina van Lengerich, Christopher Agnew, Elias M Puchner, Bo Huang, Natalia Jura
Heteromeric interactions between the catalytically impaired human epidermal growth factor receptor (HER3/ERBB3) and its catalytically active homologs EGFR and HER2 are essential for their signaling. Different ligands can activate these receptor pairs but lead to divergent signaling outcomes through mechanisms that remain largely unknown. We used stochastic optical reconstruction microscopy (STORM) with pair-correlation analysis to show that EGF and neuregulin (NRG) can induce different extents of HER3 clustering that are dependent on the nature of the coexpressed HER receptor...
April 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28304405/the-erbb3-receptor-tyrosine-kinase-negatively-regulates-paneth-cells-by-pi3k-dependent-suppression-of-atoh1
#13
Dana Almohazey, Yuan-Hung Lo, Claire V Vossler, Alan J Simmons, Jonathan J Hsieh, Edie B Bucar, Michael A Schumacher, Kathryn E Hamilton, Ken S Lau, Noah F Shroyer, Mark R Frey
Paneth cells (PCs), a secretory population located at the base of the intestinal crypt, support the intestinal stem cells (ISC) with growth factors and participate in innate immunity by releasing antimicrobial peptides, including lysozyme and defensins. PC dysfunction is associated with disorders such as Crohn's disease and necrotizing enterocolitis, but the specific pathways regulating PC development and function are not fully understood. Here we tested the role of the neuregulin receptor ErbB3 in control of PC differentiation and the ISC niche...
March 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28303795/neuregulin-1-functionalization-of-organic-fibers-for-schwann-cell-guidance
#14
Ilaria Tonazzini, Maria Moffa, Dario Pisignano, Marco Cecchini
The repair of peripheral nerve lesions is a clinical problem where the functional recovery is often far from being satisfactory, although peripheral nerves generally retain good potential for regeneration. Here, we develop a novel scaffold approach based on bioactive fibers of poly(ε-caprolactone) where nanotopographical guidance and neuregulin 1 (NRG1) cues are combined. We interface them with rat primary Schwann cells (SCs), the peripheral glial cells that drive initial regeneration of injured nerves, and found that the combination of NRG1 with parallel nano-fibrous topographies is effective in improving SC growth up to 72 h, alignment to fiber topography, and bipolar differentiation, opening original perspectives for nerve repair applications...
April 18, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28278176/cuzd1-is-a-critical-mediator-of-the-jak-stat5-signaling-pathway-that-controls-mammary-gland-development-during-pregnancy
#15
Janelle Mapes, Quanxi Li, Athilakshmi Kannan, Lavanya Anandan, Mary Laws, John P Lydon, Indrani C Bagchi, Milan K Bagchi
In the mammary gland, genetic circuits controlled by estrogen, progesterone, and prolactin, act in concert with pathways regulated by members of the epidermal growth factor family to orchestrate growth and morphogenesis during puberty, pregnancy and lactation. However, the precise mechanisms underlying the crosstalk between the hormonal and growth factor pathways remain poorly understood. We have identified the CUB and zona pellucida-like domain-containing protein 1 (CUZD1), expressed in mammary ductal and alveolar epithelium, as a novel mediator of mammary gland proliferation and differentiation during pregnancy and lactation...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28275713/axonal-type-iii-nrg1-controls-glutamate-synapse-formation-and-glua2-trafficking-in-hippocampal-accumbens-connections
#16
Chongbo Zhong, Wendy Akmentin, Chuang Du, Lorna W Role, David A Talmage
Altered neuregulin 1 (Nrg1)/ErbB signaling and glutamatergic hypofunction have been implicated in the pathophysiology of schizophrenia. Here, we employed gene chimeric ventral hippocampus (vHipp)-nucleus accumbens (nAcc) coculture from mouse, electrophysiology, immunocytochemistry, FM1-43 vesicle fusion, and electron microscopy techniques to examine the pre- and postsynaptic mechanisms of genetic deficits in Nrg1/ErbB signaling-induced glutamatergic dysfunctions. Reduced presynaptic type III Nrg1 expression along vHipp axons decreases the number of glutamate synapses and impairs GluA2 trafficking in the postsynaptic nAcc neurons, resulting in decreased frequency and amplitude of miniature EPSCs (mEPSCs)...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28273943/increased-nrg1-erbb4-signaling-in-human-symptomatic-epilepsy
#17
Jun-Ming Zhu, Ke-Xin Li, Shu-Xia Cao, Xiao-Juan Chen, Chen-Jie Shen, Ying Zhang, Hong-Yan Geng, Bi-Qing Chen, Hong Lian, Jian-Min Zhang, Xiao-Ming Li
Previous studies have shown that the neuregulin 1 (NRG1)-ErbB4 signaling pathway may regulate the excitability of fast-spiking neurons in the frontal cortex and participate in primary epilepsy pathogenesis. However, the exact roles and mechanism for NRG1/ErbB4 in human symptomatic epilepsy are still unclear. Using fresh human symptomatic epilepsy tissues, we found that the protein levels of NRG1 and ErbB4 were significantly increased in the temporal cortex. In addition, NRG1-ErbB4 signaling suppressed phosphorylation of GluN2B at position 1472 by Src kinase, and decreased levels of phosphorylation level of GluN2B and Src were detected in human symptomatic epilepsy tissues...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28271613/qiliqiangxin-protects-against-anoxic-injury-in-cardiac-microvascular-endothelial-cells-via-nrg-1-erbb-pi3k-akt-mtor-pathway
#18
Jingfeng Wang, Jingmin Zhou, Yanyan Wang, Chunjie Yang, Mingqiang Fu, Jingjing Zhang, Xueting Han, Zhiming Li, Kai Hu, Junbo Ge
Cardiac microvascular endothelial cells (CMECs) are important angiogenic components and are injured rapidly after cardiac ischaemia and anoxia. Cardioprotective effects of Qiliqiangxin (QL), a traditional Chinese medicine, have been displayed recently. This study aims to investigate whether QL could protect CMECs against anoxic injury and to explore related signalling mechanisms. CMECs were successfully cultured from Sprague-Dawley rats and exposed to anoxia for 12 hrs in the absence and presence of QL. Cell migration assay and capillary-like tube formation assay on Matrigel were performed, and cell apoptosis was determined by TUNEL assay and caspase-3 activity...
March 8, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28267150/ablation-of-neuropsin-neuregulin-1-signaling-imbalances-erbb4-inhibitory-networks-and-disrupts-hippocampal-gamma-oscillation
#19
M Kawata, S Morikawa, S Shiosaka, H Tamura
Parvalbumin-expressing interneurons are pivotal for the processing of information in healthy brain, whereas the coordination of these functions is seriously disrupted in diseased brain. How these interneurons in the hippocampus participate in pathological functions remains unclear. We previously reported that neuregulin 1 (NRG1)-ErbB4 signaling, which is actuated by neuropsin, is important for coordinating brain plasticity. Neuropsin cleaves mature NRG1 (bound to extracellular glycosaminoglycans) in response to long-term potentiation or depression, liberating a soluble ligand that activates its receptor, ErbB4...
March 7, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28263756/neuregulin-1%C3%AE-induces-proliferation-survival-and-paracrine-signaling-in-normal-human-cardiac-ventricular-fibroblasts
#20
Annet Kirabo, Sergey Ryzhov, Manisha Gupte, Seng Sengsayadeth, Richard J Gumina, Douglas B Sawyer, Cristi L Galindo
Neuregulin-1β (NRG-1β) is critical for cardiac development and repair, and recombinant forms are currently being assessed as possible therapeutics for systolic heart failure. We previously demonstrated that recombinant NRG-1β reduces cardiac fibrosis in an animal model of cardiac remodeling and heart failure, suggesting that there may be direct effects on cardiac fibroblasts. Here we show that NRG-1β receptors (ErbB2, ErbB3, and ErbB4) are expressed in normal human cardiac ventricular (NHCV) fibroblast cell lines...
March 3, 2017: Journal of Molecular and Cellular Cardiology
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