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Neuregulin

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https://www.readbyqxmd.com/read/28334857/co-cultures-with-stem-cell-derived-human-sensory-neurons-reveal-regulators-of-peripheral-myelination
#1
Alex J Clark, Malte S Kaller, Jorge Galino, Hugh J Willison, Simon Rinaldi, David L H Bennett
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...
February 15, 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
#2
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 17, 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
#3
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
#4
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...
March 20, 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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28248115/engineered-multivalency-enhances-affibody-based-her3-inhibition-and-downregulation-in-cancer-cells
#13
John S Schardt, Jinan M Oubaid, Sonya C Williams, James L Howard, Chloe M Aloimonos, Michelle L Bookstaver, Tek N Lamichhane, Sonja Sokic, Mariya S Liyasova, Maura O'Neill, Thorkell Andresson, Arif Hussain, Stanley Lipkowitz, Steven M Jay
The receptor tyrosine kinase HER3 has emerged as a therapeutic target in ovarian, prostate, breast, lung, and other cancers due to its ability to potently activate the PI3K/Akt pathway, especially via dimerization with HER2, as well as for its role in mediating drug resistance. Enhanced efficacy of HER3-targeted therapeutics would therefore benefit a wide range of patients. This study evaluated the potential of multivalent presentation, through protein engineering, to enhance the effectiveness of HER3-targeted affibodies as alternatives to monoclonal antibody therapeutics...
March 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28245533/neuregulin1-fine-tunes-pre-post-and-peri-synaptic-neuromuscular-junction-development
#14
Jiajing Wang, Fei Song, Jeffrey A Loeb
BACKGROUND: Neuromuscular junction (NMJ) development is a multistep process mediated by coordinated interactions between the nerve terminal, target muscle, and perisynaptic Schwann cell that require constant back-and-forth communication. Retrograde and anterograde growth and differentiation factors have been postulated to participate in this communication. While neuregulin1 (NRG1) has been shown to be potent anterograde signal that activates acetylcholine receptor (AChR) transcription and clustering in vitro, its roles in NMJ development in vivo remain elusive...
February 28, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28235789/erbb-signaling-attenuates-pro-inflammatory-activation-of-non-classical-monocytes
#15
Sergey Ryzhov, Anton Matafonov, Cristi L Galindo, Qinkun Zhang, Truc-Linh Tran, Daniel P Lenihan, Carrie Geisberg Lenneman, Igor Feoktistov, Douglas B Sawyer
Immune activation in chronic systolic heart failure (HF) correlates with disease severity and prognosis. Recombinant neuregulin-1 (NRG-1) is being developed as a possible therapy for HF based on activation of ERBB receptors in cardiac cells. Work in animal models of HF led us to hypothesize that there may be direct effects of NRG-1 on immune system activation and inflammation. We investigated the expression of ERBB receptors and the effect of the recombinant NRG-1 isoform glial growth factor 2 (GGF2) in subpopulations of peripheral blood mononuclear cells in subjects with HF...
February 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28230865/erbb4-signaling-stimulates-pro-inflammatory-macrophage-apoptosis-and-limits-colonic-inflammation
#16
Michael A Schumacher, Matija Hedl, Clara Abraham, Jessica K Bernard, Patricia R Lozano, Jonathan J Hsieh, Dana Almohazey, Edie B Bucar, Shivesh Punit, Peter J Dempsey, Mark R Frey
Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28228287/adipose-derived-stem-cells-combined-with-neuregulin-microparticles-for-efficient-cardiac-repair
#17
EDITORIAL
Kinam Park
No abstract text is available yet for this article.
March 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28225915/exogenous-neuregulin-1-attenuates-stz-induced-diabetic-peripheral-neuropathic-pain-in-rats
#18
Fang Zhou, Zhongyuan Xia, Kang Liu, Qin Zhou
Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed...
January 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/28208769/localisation-microscopy-of-breast-epithelial-erbb-2-receptors-and-gap-junctions-trafficking-after-%C3%AE-irradiation-neuregulin-1%C3%AE-and-trastuzumab-application
#19
Götz Pilarczyk, Ines Nesnidal, Manuel Gunkel, Margund Bach, Felix Bestvater, Michael Hausmann
In cancer, vulnerable breast epithelium malignance tendency correlates with number and activation of ErbB receptor tyrosine kinases. In the presented work, we observe ErbB receptors activated by irradiation-induced DNA injury or neuregulin- 1 β application, or alternatively, attenuated by a therapeutic antibody using high resolution fluorescence localization microscopy. The gap junction turnover coinciding with ErbB receptor activation and co-transport is simultaneously recorded. DNA injury caused by 4 Gray of 6 MeV photon γ -irradiation or alternatively neuregulin- 1 β application mobilized ErbB receptors in a nucleograde fashion-a process attenuated by trastuzumab antibody application...
February 9, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28198409/electrical-stimulation-using-conductive-polymer-polypyrrole-counters-reduced-neurite-outgrowth-of-primary-prefrontal-cortical-neurons-from-nrg1-ko-and-disc1-li-mice
#20
Qingsheng Zhang, Dorna Esrafilzadeh, Jeremy M Crook, Robert Kapsa, Elise M Stewart, Eva Tomaskovic-Crook, Gordon G Wallace, Xu-Feng Huang
Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice...
February 15, 2017: Scientific Reports
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