Gene Symbol: Nrg1
Description: neuregulin 1
Alias: pro-neuregulin-1, membrane-bound isoform, neuregulin 1 type III beta 3, pro-NRG1
Species: rat
Products:     Nrg1

Top Publications

  1. Schillo S, Pejovic V, Hunzinger C, Hansen T, Poznanovic S, Kriegsmann J, et al. Integrative proteomics: functional and molecular characterization of a particular glutamate-related neuregulin isoform. J Proteome Res. 2005;4:900-8 pubmed
    ..Here we characterize one specific isoform of neuregulin as a central biomarker for glutamate-related signaling, integrating results from in vitro and in vivo models by a differential functional and proteomic approach. ..
  2. Wang J, Frenzel K, Wen D, Falls D. Transmembrane neuregulins interact with LIM kinase 1, a cytoplasmic protein kinase implicated in development of visuospatial cognition. J Biol Chem. 1998;273:20525-34 pubmed
    ..To our knowledge, LIMK1 is the first identified protein shown to interact with the cytoplasmic tail of a receptor tyrosine kinase ligand. ..
  3. Okada M, Corfas G. Neuregulin1 downregulates postsynaptic GABAA receptors at the hippocampal inhibitory synapse. Hippocampus. 2004;14:337-44 pubmed
    The growth factor neuregulin 1 (NRG1) has been proposed to contribute to the formation and maturation of neuromuscular and interneuronal synapses by upregulating the expression of specific neurotransmitter receptor subunits...
  4. Gambarotta G, Garzotto D, Destro E, Mautino B, Giampietro C, Cutrupi S, et al. ErbB4 expression in neural progenitor cells (ST14A) is necessary to mediate neuregulin-1beta1-induced migration. J Biol Chem. 2004;279:48808-16 pubmed
    ..Our data show that ErbB4 signaling via PI3K activation plays a fundamental role in controlling NRG1beta1-induced migration. ..
  5. Wen D, Suggs S, Karunagaran D, Liu N, Cupples R, Luo Y, et al. Structural and functional aspects of the multiplicity of Neu differentiation factors. Mol Cell Biol. 1994;14:1909-19 pubmed
    ..Taken together, these results suggest that different NDF isoforms are generated by alternative splicing and perform distinct tissue-specific functions. ..
  6. Zhao Y, Sawyer D, Baliga R, Opel D, Han X, Marchionni M, et al. Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem. 1998;273:10261-9 pubmed
    Neuregulins (i.e. neuregulin-1 (NRG1), also called neu differentiation factor, heregulin, glial growth factor, and acetylcholine receptor-inducing activity) are known to induce growth and differentiation of epithelial, glial, neuronal, ..
  7. Taveggia C, Thaker P, Petrylak A, Caporaso G, Toews A, Falls D, et al. Type III neuregulin-1 promotes oligodendrocyte myelination. Glia. 2008;56:284-93 pubmed
    ..this study, we have examined the regulation of oligodendrocyte myelination by the type III isoform of neuregulin-1 (NRG1), a neuronal signal essential for Schwann cell differentiation and myelination...
  8. Montero J, Rodríguez Barrueco R, Ocana A, Diaz Rodriguez E, Esparís Ogando A, Pandiella A. Neuregulins and cancer. Clin Cancer Res. 2008;14:3237-41 pubmed publisher
    ..Therefore, targeting of the neuregulins may be helpful in neoplastic diseases in which these polypeptide factors contribute to tumor generation and/or maintenance. ..
  9. Fukazawa R, Miller T, Kuramochi Y, Frantz S, Kim Y, Marchionni M, et al. Neuregulin-1 protects ventricular myocytes from anthracycline-induced apoptosis via erbB4-dependent activation of PI3-kinase/Akt. J Mol Cell Cardiol. 2003;35:1473-9 pubmed
    ..Treatment with the erbB2 antibody had no effect on anthracycline-induced apoptosis. Thus, NRG-1beta protects against anthracycline-induced apoptosis via erbB4-dependent activation of the PI3-kinase/Akt pathway. ..

More Information


  1. Wolpowitz D, Mason T, Dietrich P, Mendelsohn M, Talmage D, Role L. Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses. Neuron. 2000;25:79-91 pubmed
  2. Frohnert P, Stonecypher M, Carroll S. Constitutive activation of the neuregulin-1/ErbB receptor signaling pathway is essential for the proliferation of a neoplastic Schwann cell line. Glia. 2003;43:104-18 pubmed
    ..The absence of EGFR expression in JS1 cells suggests that constitutive activation of the NRG-1/erbB signaling pathway is an alternative means of inducing Schwann cell neoplasia. ..
  3. Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, et al. Neuregulin-1 type III determines the ensheathment fate of axons. Neuron. 2005;47:681-94 pubmed
    ..We now report that threshold levels of neuregulin-1 (NRG1) type III on axons determine their ensheathment fate...
  4. Audisio C, Raimondo S, Nicolino S, Gambarotta G, Di Scipio F, Macrì L, et al. Morphological and biomolecular characterization of the neonatal olfactory bulb ensheathing cell line. J Neurosci Methods. 2009;185:89-98 pubmed publisher
    ..showed that NOBECs express the glial markers S100, GFAP (Glial Fibrillar Acid Protein) and p75NGFR as well as NRG1 (neuregulin-1) and ErbB1-2-3 receptors; while they are negative for ErbB4...
  5. Hansen M, Roehm P, Chatterjee P, Green S. Constitutive neuregulin-1/ErbB signaling contributes to human vestibular schwannoma proliferation. Glia. 2006;53:593-600 pubmed
    ..We have previously shown that VSs produce the glial growth factor, neuregulin-1 (NRG1), and its receptors, ErbB2 and ErbB3...
  6. Lemmens K, Segers V, Demolder M, De Keulenaer G. Role of neuregulin-1/ErbB2 signaling in endothelium-cardiomyocyte cross-talk. J Biol Chem. 2006;281:19469-77 pubmed
    ..Cardiac NRG-1 synthesis occurs in endothelial cells adjacent to cardiac myocytes and is sensitive to factors related to the regulation of blood pressure. ..
  7. Wen D, Peles E, Cupples R, Suggs S, Bacus S, Luo Y, et al. Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. Cell. 1992;69:559-72 pubmed
    ..Northern blot analysis indicated the existence of several NDF transcripts, the major ones being 1.8, 2.6, and 6.7 kb in size. Transformation by the ras oncogene dramatically elevated the expression of NDF in fibroblasts. ..
  8. Michailov G, Sereda M, Brinkmann B, Fischer T, Haug B, Birchmeier C, et al. Axonal neuregulin-1 regulates myelin sheath thickness. Science. 2004;304:700-3 pubmed
    ..We use mutant and transgenic mouse lines to show that axonal Neuregulin-1 (Nrg1) signals information about axon size to Schwann cells...
  9. Viehover A, Miller R, Park S, Fischbach G, Vartanian T. Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions. Dev Neurosci. 2001;23:377-86 pubmed
    ..In active and chronic active MS lesions, however, the expression of astrocyte neuregulin is dramatically reduced. The absence of neuregulin in active MS lesions may contribute to the paucity of remyelination in MS. ..
  10. Gui C, Zhu L, Hu M, Lei L, Long Q. Neuregulin-1/ErbB signaling is impaired in the rat model of diabetic cardiomyopathy. Cardiovasc Pathol. 2012;21:414-20 pubmed publisher
    ..The neuregulin-1(NRG1)/ErbB signal system plays a critical role in maintenance of adult heart function...
  11. Kerber G, Streif R, Schwaiger F, Kreutzberg G, Hager G. Neuregulin-1 isoforms are differentially expressed in the intact and regenerating adult rat nervous system. J Mol Neurosci. 2003;21:149-65 pubmed
    ..The splice variants beta2 and beta4 display an initial downregulation of mRNA levels, followed by an increase during the period of axon remyelination. Thus, Nrg- 1-beta2 and -beta4 might be involved in myelination. ..
  12. Leimeroth R, Lobsiger C, Lüssi A, Taylor V, Suter U, Sommer L. Membrane-bound neuregulin1 type III actively promotes Schwann cell differentiation of multipotent Progenitor cells. Dev Biol. 2002;246:245-58 pubmed
    Many steps of peripheral glia development appear to be regulated by neuregulin1 (NRG1) signaling but the exact roles of the different NRG1 isoforms in these processes remain to be determined...
  13. Zhao W, Ren S. Neuregulin-1 (Nrg1) is mainly expressed in rat pituitary gonadotroph cells and possibly regulates prolactin (PRL) secretion in a juxtacrine manner. J Neuroendocrinol. 2011;23:1252-62 pubmed publisher
    The binding of Neuregulin-1 (Nrg1) to its cognate receptors ErbB-3 and -4 mediates intercellular and intracellular communication. In vitro, this interaction has been shown to control prolactin (PRL) secretion from pituitary tumour cells...
  14. Shirakabe K, Wakatsuki S, Kurisaki T, Fujisawa Sehara A. Roles of Meltrin beta /ADAM19 in the processing of neuregulin. J Biol Chem. 2001;276:9352-8 pubmed
    ..Furthermore, the effects of the secretory pathway inhibitors suggested that meltrin beta participates in the intracellular processing of NRGs rather than the cleavage on the cell surface. ..
  15. Danovi D, Cremona C, Machado da Silva G, Basu S, Noon L, Parrinello S, et al. A genetic screen for anchorage-independent proliferation in mammalian cells identifies a membrane-bound neuregulin. PLoS ONE. 2010;5:e11774 pubmed publisher
    ..This novel transforming mechanism may provide new targets for cancer therapy. ..
  16. Linying Z, Wei W, Minxia W, Wenmin Z, Liangcheng Z. Neuroprotective effects of neuregulin-1 ß on oligodendrocyte type 2 astrocyte progenitors following oxygen and glucose deprivation. Pediatr Neurol. 2014;50:357-62 pubmed publisher
    ..These results suggest that neuregulin-1ß could protect the oligodendrocyte type 2 astrocyte progenitors against hypoxic injury, and the mechanism may be associated with the PI3K-Akt signaling pathway. ..
  17. Joung I, Yoo M, Woo J, Chang C, Heo H, Kwon Y. Secretion of EGF-like domain of heregulin? promotes axonal growth and functional recovery of injured sciatic nerve. Mol Cells. 2010;30:477-84 pubmed publisher
    Neuregulin 1 (NRG1) and epidermal growth factor receptor (ErbB) signaling pathways control Schwann cells during axonal regeneration in an injured peripheral nervous system...
  18. Fornasari B, El Soury M, De Marchis S, Perroteau I, Geuna S, Gambarotta G. Neuregulin1 alpha activates migration of neuronal progenitors expressing ErbB4. Mol Cell Neurosci. 2016;77:87-94 pubmed publisher
    ..The ligand neuregulin1 (NRG1) and its receptor ErbB4 are genes conferring susceptibility to schizophrenia, playing a key role in the control of ..
  19. Kim H, Cho S, Lee C, Jeong S. Neuregulin 1 as an endogenous regulator of nicotinic acetylcholine receptors in adult major pelvic ganglion neurons. Biochem Biophys Res Commun. 2015;463:632-7 pubmed publisher
    We investigated whether endogenous neuregulin 1 (NRG1) is released in a soluble form (called sNRG1) and upregulates expression of nicotinic acetylcholine receptor (nAChR) in autonomic major pelvic ganglion (MPG) neurons of adult rats...
  20. Syed N, Reddy K, Yang D, Taveggia C, Salzer J, Maurel P, et al. Soluble neuregulin-1 has bifunctional, concentration-dependent effects on Schwann cell myelination. J Neurosci. 2010;30:6122-31 pubmed publisher
    Members of the neuregulin-1 (Nrg1) growth factor family play important roles during Schwann cell development. Recently, it has been shown that the membrane-bound type III isoform is required for Schwann cell myelination...
  21. Bare D, Becker Catania S, DeVries G. Differential localization of neuregulin-1 type III in the central and peripheral nervous system. Brain Res. 2011;1369:10-20 pubmed publisher
    In the developing PNS, axonal neuregulin-1 (NRG1) type III is the key determinant for myelination. However, the specific role for NRG1 (III) in the CNS has not been established...
  22. Jang H, Han D, Yuk S. Changes of neuregulin-1 (NRG-1) expression in a rat model of overactive bladder induced by partial urethral obstruction: is NRG-1 a new biomarker of overactive bladder?. BMC Urol. 2013;13:54 pubmed publisher
    ..The study suggests that NRG-1 is a potential new biomarker of OAB; the urothelium might be a therapeutic target for OAB treatment. ..
  23. Calaora V, Rogister B, Bismuth K, Murray K, Brandt H, Leprince P, et al. Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro. J Neurosci. 2001;21:4740-51 pubmed
    ..We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs. ..
  24. Ieguchi K, Fujita M, Ma Z, Davari P, Taniguchi Y, Sekiguchi K, et al. Direct binding of the EGF-like domain of neuregulin-1 to integrins ({alpha}v{beta}3 and {alpha}6{beta}4) is involved in neuregulin-1/ErbB signaling. J Biol Chem. 2010;285:31388-98 pubmed publisher
    ..We discovered that neuregulin-1 (NRG1), either as an isolated EGF-like domain or as a native multi-domain form, binds to integrins ?v?3 (with a K(D) of 1...
  25. Gonzalez Noriega A, Michalak C, Antonio Sosa Melgarejo J. Cation-independent mannose 6-phosphate and 78 kDa receptors for lysosomal enzyme targeting are located in different cell compartments. Biochim Biophys Acta. 2005;1745:7-19 pubmed
    ..Results obtained suggest that the 78 kDa receptor is found along the endocytic pathway, but in vesicles different from the cation-independent mannose 6-phosphate receptor. ..
  26. Cahill M, Remmers C, Jones K, Xie Z, Sweet R, Penzes P. Neuregulin1 signaling promotes dendritic spine growth through kalirin. J Neurochem. 2013;126:625-35 pubmed publisher
    The biological functions of the neuregulin 1 (NRG1) and ERBB4 genes have received much recent attention due to several studies showing associations between these genes and schizophrenia...
  27. Iaci J, Ganguly A, Finklestein S, Parry T, Ren J, Saha S, et al. Glial growth factor 2 promotes functional recovery with treatment initiated up to 7 days after permanent focal ischemic stroke. Neuropharmacology. 2010;59:640-9 pubmed publisher
  28. Li H, Chou S, Hamasaki T, Perez Garcia C, O Leary D. Neuregulin repellent signaling via ErbB4 restricts GABAergic interneurons to migratory paths from ganglionic eminence to cortical destinations. Neural Dev. 2012;7:10 pubmed publisher
    ..if not all, migrating MGE-derived INs express the neuregulin (NRG) receptor, ErbB4, we investigated influences of Nrg1 isoforms and Nrg3 on IN migration through ventral telencephalon (vTel) and within cortex...
  29. Safa R, Peng X, Pentassuglia L, Lim C, Lamparter M, Silverstein C, et al. Neuregulin-1? regulation of embryonic endothelial progenitor cell survival. Am J Physiol Heart Circ Physiol. 2011;300:H1311-9 pubmed publisher
    ..NRG does not induce eEPC proliferation or migration but does protect eEPCs against serum deprivation-induced apoptosis. These results suggest a role for tissue-derived NRG in the regulation of EPC survival. ..
  30. Kramer R, Bucay N, Kane D, Martin L, Tarpley J, Theill L. Neuregulins with an Ig-like domain are essential for mouse myocardial and neuronal development. Proc Natl Acad Sci U S A. 1996;93:4833-8 pubmed
    ..The trigeminal ganglion is reduced in size and lacks projections toward the brain stem and mandible. We conclude that IgL-domain-containing neuregulins play a major role in cardiac and neuronal development. ..
  31. Morano M, Angotti C, Tullio F, Gambarotta G, Penna C, Pagliaro P, et al. Myocardial ischemia/reperfusion upregulates the transcription of the Neuregulin1 receptor ErbB3, but only postconditioning preserves protein translation: Role in oxidative stress. Int J Cardiol. 2017;233:73-79 pubmed publisher
    Neuregulin1 (Nrg1) and its receptors ErbB are crucial for heart development and for adult heart structural maintenance and function and Nrg1 has been proposed for heart failure treatment...
  32. Basak S, Desai D, Rho E, Ramos R, Maurel P, Kim H. E-cadherin enhances neuregulin signaling and promotes Schwann cell myelination. Glia. 2015;63:1522-36 pubmed publisher
    ..When over-expressed in Schwann cells, E-cadherin improves myelination on Nrg1 type III(+/-) neurons and induces myelination on normally non-myelinated axons of sympathetic neurons...
  33. Allison J, Das P, Ma J, Inglis F, Jones F. The ERBB4 intracellular domain (4ICD) regulates NRG1-induced gene expression in hippocampal neurons. Neurosci Res. 2011;70:155-63 pubmed publisher
    The NRG1 growth factor and ERBB4 receptor have been identified as leading schizophrenia risk genes...
  34. Kanzaki H, Mizobuchi S, Obata N, Itano Y, Kaku R, Tomotsuka N, et al. Expression changes of the neuregulin 1 isoforms in neuropathic pain model rats. Neurosci Lett. 2012;508:78-83 pubmed publisher
    The neuregulin1 (Nrg1) gene that is expressed in the dorsal root ganglion (DRG) contains an EGF-like domain, which is known to be a direct ligand for ErbB3 and ErbB4...
  35. Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development. Nature. 1995;378:386-90 pubmed
    ..All cell types affected by the mutation express either erbB3 or erbB4, indicating that either of these tyrosine kinase receptors can be a component in recognition and transmission of essential neuregulin signals. ..
  36. Canto C, Suárez E, Lizcano J, Griñó E, Shepherd P, Fryer L, et al. Neuregulin signaling on glucose transport in muscle cells. J Biol Chem. 2004;279:12260-8 pubmed
    ..The PI3K, PDK1, and PKCzeta pathway can be considered as an alternative mechanism, independent of insulin, to induce glucose uptake. ..
  37. Geuna S, Nicolino S, Raimondo S, Gambarotta G, Battiston B, Tos P, et al. Nerve regeneration along bioengineered scaffolds. Microsurgery. 2007;27:429-38 pubmed
    ..and progressive increase in the expression of NRG1alpha isoform only, while the appearance of the beta isoform of NRG1, which is normally present in peripheral nerves, was delayed...
  38. Keely S, Barrett K. ErbB2 and ErbB3 receptors mediate inhibition of calcium-dependent chloride secretion in colonic epithelial cells. J Biol Chem. 1999;274:33449-54 pubmed
    ..Differential dimerization with other ErbB family members may underlie the ability of the EGFR to propagate diverse inhibitory signals in response to activation by EGF or transactivation by CCh. ..
  39. Fregnan F, Gnavi S, Macrì L, Perroteau I, Gambarotta G. The four isoforms of the tyrosine kinase receptor ErbB4 provide neural progenitor cells with an adhesion preference for the transmembrane type III isoform of the ligand neuregulin 1. Neuroreport. 2014;25:233-41 pubmed publisher
    ..We found that each of the four ErbB4 isoforms is able to confer cells with an adhesion preference for cells expressing the transmembrane neuregulin 1 type III. ..
  40. Jevsek M, Jaworski A, Polo Parada L, Kim N, Fan J, Landmesser L, et al. CD24 is expressed by myofiber synaptic nuclei and regulates synaptic transmission. Proc Natl Acad Sci U S A. 2006;103:6374-9 pubmed
    ..Because CD24 is also expressed in some neurons, additional experiments will be required to determine whether pre- or postsynaptic CD24 mediates these effects on presynaptic development and function. ..
  41. Iwakura Y, Wang R, Inamura N, Araki K, Higashiyama S, Takei N, et al. Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons. PLoS ONE. 2017;12:e0174780 pubmed publisher
    The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation...
  42. Ozkaynak E, Abello G, Jaegle M, van Berge L, Hamer D, Kegel L, et al. Adam22 is a major neuronal receptor for Lgi4-mediated Schwann cell signaling. J Neurosci. 2010;30:3857-64 pubmed publisher
    ..Our results thus reveal a novel paracrine signaling axis in peripheral nerve myelination in which Schwann cell secreted Lgi4 functions through binding of axonal Adam22 to drive the differentiation of Schwann cells. ..
  43. Nicolino S, Panetto A, Raimondo S, Gambarotta G, Guzzini M, Fornaro M, et al. Denervation and reinnervation of adult skeletal muscle modulate mRNA expression of neuregulin-1 and ErbB receptors. Microsurgery. 2009;29:464-72 pubmed publisher
    ..analyses, in an in vivo model of adult skeletal muscle denervation/reinnervation, that expression of Neuregulin1 (NRG1) and ErbB receptors is regulated by the innervation condition...
  44. Ledonne A, Nobili A, Latagliata E, Cavallucci V, Guatteo E, Puglisi Allegra S, et al. Neuregulin 1 signalling modulates mGluR1 function in mesencephalic dopaminergic neurons. Mol Psychiatry. 2015;20:959-73 pubmed publisher
    Neuregulin 1 (NRG1) is a trophic factor that has an essential role in the nervous system by modulating neurodevelopment, neurotransmission and synaptic plasticity...
  45. Balañá M, Lupu R, Labriola L, Charreau E, Elizalde P. Interactions between progestins and heregulin (HRG) signaling pathways: HRG acts as mediator of progestins proliferative effects in mouse mammary adenocarcinomas. Oncogene. 1999;18:6370-9 pubmed
    ..These results provide the first evidence of interactions between progestins and HRB/ErbB signal transduction pathways in mammary cancer and the first demonstration that IGF-IR is required for HRG proliferative effects. ..
  46. Middle F, Pritchard A, Handoko H, Haque S, Holder R, Bentham P, et al. No association between neuregulin 1 and psychotic symptoms in Alzheimer's disease patients. J Alzheimers Dis. 2010;20:561-7 pubmed publisher
    ..Variants within the neuregulin-1 (NRG1) gene have been investigated both in early onset psychiatric disorders, such as schizophrenia and recently in AD ..
  47. Rosenbaum C, Karyala S, Marchionni M, Kim H, Krasnoselsky A, Happel B, et al. Schwann cells express NDF and SMDF/n-ARIA mRNAs, secrete neuregulin, and show constitutive activation of erbB3 receptors: evidence for a neuregulin autocrine loop. Exp Neurol. 1997;148:604-15 pubmed
    ..These data implicate both paracrine and autocrine pathways involving neuregulin form(s) in Schwann cell mitogenic responses. ..
  48. Taylor A, Taylor S, Koenig J. The involvement of Type II Neuregulin-1 in rat visuospatial learning and memory. Neurosci Lett. 2012;531:131-5 pubmed publisher
    ..Here, we have utilized a rat model (Nrg1(Tn)), which is hypomorphic for the neuregulin-1 (Nrg1) gene, to test whether reduced Type II NRG1 in the rat brain ..
  49. Edwards J, Bottenstein J. Neuregulin 1 growth factors regulate proliferation but not apoptosis of a CNS neuronal progenitor cell line. Brain Res. 2006;1108:63-75 pubmed
    ..Although several of these growth factors have been identified, high levels of neuregulin 1 (NRG1) mRNA and protein expression in the CNS during the time of neuronal progenitor expansion suggest NRG1 growth ..
  50. Chen Y, Johnson M, Lieberman M, Goodchild R, Schobel S, Lewandowski N, et al. Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components. J Neurosci. 2008;28:6872-83 pubmed publisher
    Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene...
  51. Yu H, Park W, Nam K, Song D, Kim H, Baik T, et al. Neuregulin 1 Controls Glutamate Uptake by Up-regulating Excitatory Amino Acid Carrier 1 (EAAC1). J Biol Chem. 2015;290:20233-44 pubmed publisher
    Neuregulin 1 (NRG1) is a trophic factor that is thought to have important roles in the regulating brain circuitry. Recent studies suggest that NRG1 regulates synaptic transmission, although the precise mechanisms remain unknown...
  52. Lee H, Akita R, Sliwkowski M, Maihle N. A naturally occurring secreted human ErbB3 receptor isoform inhibits heregulin-stimulated activation of ErbB2, ErbB3, and ErbB4. Cancer Res. 2001;61:4467-73 pubmed
  53. Wang G, Dai D, Chen X, Yuan L, Zhang A, Lu Y, et al. Upregulation of neuregulin-1 reverses signs of neuropathic pain in rats. Int J Clin Exp Pathol. 2014;7:5916-21 pubmed provided a potential molecular mechanism; large dorsal root ganglion (DRG) neurons secrete neuregulin-1 (NRG1), which binds to erbB4 receptors on interneurons and promotes GABA release to inhibit C-fiber-evoked nociceptive ..
  54. Matsukawa R, Hirooka Y, Ito K, Honda N, Sunagawa K. Central neuregulin-1/ErbB signaling modulates cardiac function via sympathetic activity in pressure overload-induced heart failure. J Hypertens. 2014;32:817-25 pubmed publisher
    ..Activation of central NRG-1 signaling improves cardiac function through sympathoinhibition. These findings provide a new treatment concept and support the benefit of NRG-1 treatment in heart failure. ..
  55. Chaudhury A, Gerecke K, Wyss J, Morgan D, Gordon M, Carroll S. Neuregulin-1 and erbB4 immunoreactivity is associated with neuritic plaques in Alzheimer disease brain and in a transgenic model of Alzheimer disease. J Neuropathol Exp Neurol. 2003;62:42-54 pubmed
  56. Li Q, Zhang R, Guo Y, Mei Y. Effect of neuregulin on apoptosis and expressions of STAT3 and GFAP in rats following cerebral ischemic reperfusion. J Mol Neurosci. 2009;37:67-73 pubmed publisher
    ..05). NRG-1beta may play a neuroprotective role in cerebral ischemic insult by activating JAK/STAT signal transduction pathway, promoting the astrocyte gumnosis and regulating the anti-apoptosis mechanism in neurocytes. ..
  57. Schmid R, McGrath B, Berechid B, Boyles B, Marchionni M, Sestan N, et al. Neuregulin 1-erbB2 signaling is required for the establishment of radial glia and their transformation into astrocytes in cerebral cortex. Proc Natl Acad Sci U S A. 2003;100:4251-6 pubmed
    ..These results suggest that developmental changes in NRG-1-erbB2 interactions modulate the establishment of radial glia and contribute to their appropriate transformation into astrocytes. ..
  58. Fried K, Risling M, Tidcombe H, Gassmann M, Lillesaar C. Expression of ErbB3, ErbB4, and neuregulin-1 mRNA during tooth development. Dev Dyn. 2002;224:356-60 pubmed
    ..The results suggest that ErbB3 and ErbB4 may participate in tooth morphogenesis. The specific interactions between NRG isoforms and ErbB receptors during this process remain to be determined. ..
  59. Parkinson D, Langner K, Namini S, Jessen K, Mirsky R. beta-Neuregulin and autocrine mediated survival of Schwann cells requires activity of Ets family transcription factors. Mol Cell Neurosci. 2002;20:154-67 pubmed
    ..These data demonstrate that distinct autocrine and beta-neuregulin survival signals converge in their requirement for Ets dependent transcription in Schwann cell survival. ..
  60. Giraud M, Fluck M, Zuppinger C, Suter T. Expressional reprogramming of survival pathways in rat cardiocytes by neuregulin-1beta. J Appl Physiol (1985). 2005;99:313-22 pubmed
    ..These MAPK-dependent expressional adjustments point to novel oxidative defense and hypertrophy pathways being involved in the longer lasting protective function of neuregulin in the heart. ..
  61. Go R, Perry R, Wiener H, Bassett S, Blacker D, Devlin B, et al. Neuregulin-1 polymorphism in late onset Alzheimer's disease families with psychoses. Am J Med Genet B Neuropsychiatr Genet. 2005;139B:28-32 pubmed
    ..schizophrenia, in the Icelandic population identified a risk haplotype within the 5' region of neuregulin-1 (NRG1) on 8p12...
  62. Rio C, Rieff H, Qi P, Khurana T, Corfas G. Neuregulin and erbB receptors play a critical role in neuronal migration. Neuron. 1997;19:39-50 pubmed
    ..Moreover, soluble NRG is as effective as neuron-glia contact in the induction of radial glia formation. These results suggest that the activation of glial erbB4 by NRG is an early critical step in the neuronal migration program. ..
  63. Sandrock A, Dryer S, Rosen K, Gozani S, Kramer R, Theill L, et al. Maintenance of acetylcholine receptor number by neuregulins at the neuromuscular junction in vivo. Science. 1997;276:599-603 pubmed
    ..Thus, the density of AChRs in the postsynaptic membrane depends on immunoglobulin-containing neuregulin isoforms throughout the life of the animal. ..
  64. Liao H, Keller S, Castle J. Insulin-regulated aminopeptidase marks an antigen-stimulated recycling compartment in mast cells. Traffic. 2006;7:155-67 pubmed
    ..We propose that IRAP vesicles represent a second IgE-sensitive exocytotic compartment in mast cells, which is regulated differently from secretory granules, and that these vesicles may be similar to GLUT4 vesicles. ..
  65. Taylor S, Taylor A, Koenig J. The interaction of disrupted type II neuregulin 1 and chronic adolescent stress on adult anxiety- and fear-related behaviors. Neuroscience. 2013;249:31-42 pubmed publisher
    ..Neuregulin 1 (NRG1) is a frequently identified schizophrenia susceptibility gene that has also been associated with the psychotic ..
  66. Riese D, Kim E, Elenius K, Buckley S, Klagsbrun M, Plowman G, et al. The epidermal growth factor receptor couples transforming growth factor-alpha, heparin-binding epidermal growth factor-like factor, and amphiregulin to Neu, ErbB-3, and ErbB-4. J Biol Chem. 1996;271:20047-52 pubmed
    ..Therefore, EGF, TGF-alpha, AR, and HB-EGF are functionally identical in this model system and behave differently from the EGF family hormones betacellulin and neuregulins. ..
  67. Limpert A, Carter B. Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation. J Biol Chem. 2010;285:16614-22 pubmed publisher
    ..membranes are sufficient to promote NF-kappaB activation in cultured Schwann cells and identify neuregulin 1 (NRG1), specifically the membrane-bound type III isoform, as the signal responsible for activating this transcription ..
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    ..ErbB2 and ErbB4 receptors re-localized to cardiac myocyte nuclei in failing type 1 diabetic post-MI hearts. Type 1 DM prevents compensatory up-regulation of myocardial NRG-1/ErbB after MI coincident with an increased severity of HF. ..
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    ..Direct interaction between heregulin and the two proteins was demonstrated by chemical cross-linking experiments using 125I-heregulin followed by immunoprecipitation with antibodies specific for erbB2 or erbB3. ..
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    ..Moreover, genetic linkage and post mortem studies strongly suggest a role for altered neuregulin 1 (Nrg1)/erbB4 signaling in schizophrenia pathology...
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    ..The data in this study imply that NRG-1? promotes neurite outgrowth and neuronal migration from DRG explants in vitro. ..
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    ..Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1?. These data provide new insights of the actions of NRG-1? in sensory neurons. ..
  73. Erickson S, O Shea K, Ghaboosi N, Loverro L, Frantz G, Bauer M, et al. ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice. Development. 1997;124:4999-5011 pubmed
    ..Numerous organs, including the stomach and pancreas also exhibited anomalous development. ..
  74. Fledrich R, Stassart R, Klink A, Rasch L, Prukop T, Haag L, et al. Soluble neuregulin-1 modulates disease pathogenesis in rodent models of Charcot-Marie-Tooth disease 1A. Nat Med. 2014;20:1055-61 pubmed publisher
    ..We demonstrate that enhanced PI3K-Akt signaling by axonally overexpressed neuregulin-1 (NRG1) type I drives diseased Schwann cells toward differentiation and preserves peripheral nerve axons...
  75. Shyu W, Lin S, Chiang M, Yang H, Thajeb P, Li H. Neuregulin-1 reduces ischemia-induced brain damage in rats. Neurobiol Aging. 2004;25:935-44 pubmed
    ..NRG-1 reduced ischemia/reperfusion injury, indicating that it may act as an endogenous neuroprotective factor against stroke. Therefore, NRG-1 may represent a target for the development of new treatments for stroke. ..
  76. Kim H, Lee C, Cho S, Whang K, Cha B, Shin J, et al. Neuregulin 1 up-regulates the expression of nicotinic acetylcholine receptors through the ErbB2/ErbB3-PI3K-MAPK signaling cascade in adult autonomic ganglion neurons. J Neurochem. 2013;124:502-13 pubmed publisher
    We investigated effects of Neuregulin 1 (NRG1) on the expression of nicotinic acetylcholine receptor (nAChR) in major pelvic ganglion (MPG) from adult rat...
  77. Calvo M, Zhu N, Tsantoulas C, Ma Z, Grist J, Loeb J, et al. Neuregulin-ErbB signaling promotes microglial proliferation and chemotaxis contributing to microgliosis and pain after peripheral nerve injury. J Neurosci. 2010;30:5437-50 pubmed publisher
    ..Microglia express the NRG1 receptors erbB2, 3, and 4, and NRG1 signaling via the erbB2 receptor stimulated microglial proliferation, ..
  78. Pirotte D, Wislet Gendebien S, Cloes J, Rogister B. Neuregulin-1 modulates the differentiation of neural stem cells in vitro through an interaction with the Swi/Snf complex. Mol Cell Neurosci. 2010;43:72-80 pubmed publisher
    ..Moreover, we showed that ICD physically interacted in cultured NSC with BRM and BAF57, two members of the Swi/Snf remodeling complex, and that ICD stimulation of neuronal cell differentiation is dependent on the presence of BAF57. ..
  79. Cotter L, Ozcelik M, Jacob C, Pereira J, Locher V, Baumann R, et al. Dlg1-PTEN interaction regulates myelin thickness to prevent damaging peripheral nerve overmyelination. Science. 2010;328:1415-8 pubmed publisher
    ..Indeed, the Dlg1 brake is no longer functional in a mouse model of Charcot-Marie-Tooth disease. Therefore, negative regulation of myelination appears to be essential for optimization of nerve conduction velocity and myelin maintenance. ..
  80. Hamra F, Chapman K, Nguyen D, Garbers D. Identification of neuregulin as a factor required for formation of aligned spermatogonia. J Biol Chem. 2007;282:721-30 pubmed
    ..In fact, SNL cells were found to express 100-fold higher levels of neuregulin-1 transcripts than MSC-1 cells. Thus, we identify neuregulin as a factor required for spermatogonial amplification and differentiation in culture. ..