Neuregulin 1
| Neuregulin 1 | |||||||||||||
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File:PBB Protein NRG1 image.jpg PDB rendering based on 1hae. | |||||||||||||
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| Symbols | NRG1 ; ARIA; GGF; GGF2; HGL; HRG; HRG1; HRGA; NDF; SMDF | ||||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 8509 | ||||||||||||
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| File:PBB GE NRG1 206343 s at tn.png | |||||||||||||
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Neuregulin 1 or NRG1 is one of the four proteins of the neuregulin family which act on EGFR family of receptors. Neuregulin 1 is produced in numerous isoforms by alternative splicing, and this allows it to perform a wide variety of functions. Neuregulin 1-ErbB4 interactions are thought to play a role in the pathological mechanism of schizophrenia.[1] The protein also has a putative ability to protect the brain from damage induced by stroke.[2]
By 2004, six major isoforms of neuregulin 1 were known:
- Type I NRG1; alternative names: Heregulin, NEU differentiation factor (NDF), or acetylcholine receptor inducing activity (ARIA)
- Type II NRG1; alternative name: Glial Growth Factor-2 (GGF2);
- Type III NRG1; alternative name: Sensory and motor neuron-derived factor (SMDF);
- Type IV NRG1;
- Type V NRG1;
- Type VI NRG1; Types IV-VI are proteins with 3 novel N-terminal domains identified in 2004.[3]
Link to schizophrenia
A number of studies have provided evidence of NRG1 gene relation to schizophrenia.[1][4] High-risk deCODE (Icelandic) haplotype was discovered in 2002 on the 5'-end of the gene by Stefansson et al.[5] The SNP8NRG243177 allele from this haplotype was associated in 2006 with a heightened expression of the Type IV NRG1 in the brains of people suffering from schizophrenia.[6][7]
References
- ↑ 1.0 1.1 Li D, Collier DA, He L. (2006) Meta-analysis shows strong positive association of the neuregulin 1 (NRG1) gene with schizophrenia. Hum Mol Genet; 15(12):1995-2002. PMID 16687441
- ↑ Xu Z, Croslan DR, Harris AE, Ford GD, Ford BD (2006). "Extended therapeutic window and functional recovery after intraarterial administration of neuregulin-1 after focal ischemic stroke". J. Cereb. Blood Flow Metab. 26 (4): 527–35. doi:10.1038/sj.jcbfm.9600212. PMID 16136057.
- ↑ Steinthorsdottir V, Stefansson H, Ghosh S, Birgisdottir B, Bjornsdottir S, Fasquel AC, Olafsson O, Stefansson K, Gulcher JR (2004). "Multiple novel transcription initiation sites for NRG1". Gene. 342 (1): 97–105. doi:10.1016/j.gene.2004.07.029. PMID 15527969.
- ↑ Gene Overview of All Published Schizophrenia-Association Studies for NRG1- SchizophreniaGene database, Schizophrenia Research Forum.
- ↑ Stefansson H, Sigurdsson E, Steinthorsdottir V, Bjornsdottir S, Sigmundsson T, Ghosh S, Brynjolfsson J, Gunnarsdottir S, Ivarsson O, Chou TT, Hjaltason O, Birgisdottir B, Jonsson H, Gudnadottir VG, Gudmundsdottir E, Bjornsson A, Ingvarsson B, Ingason A, Sigfusson S, Hardardottir H, Harvey RP, Lai D, Zhou M, Brunner D, Mutel V, Gonzalo A, Lemke G, Sainz J, Johannesson G, Andresson T, Gudbjartsson D, Manolescu A, Frigge ML, Gurney ME, Kong A, Gulcher JR, Petursson H, Stefansson K.(2002) Neuregulin 1 and susceptibility to schizophrenia. Am J Hum Genet. 71(4):877-92 PMID 12145742 free full text
- ↑ Law AJ, Lipska BK, Weickert CS, Hyde TM, Straub RE, Hashimoto R, Harrison PJ, Kleinman JE, Weinberger DR. (2006) Neuregulin 1 transcripts are differentially expressed in schizophrenia and regulated by 5' SNPs associated with the disease. Proc Natl Acad Sci U S A. 103(17):6747-52. PMID 16618933 free full text
- ↑ Hall J, Whalley HC, Job DE, Baig BJ, McIntosh AM, Evans KL, Thomson PA, Porteous DJ, Cunningham-Owens DG, Johnstone EC, Lawrie SM. (2006) A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms. Nat Neurosci. 9(12):1477-8. doi:10.1038/nn1795 PMID 17072305
Further reading
- Lupu R, Lippman ME (1994). "William L. McGuire Memorial Symposium. The role of erbB2 signal transduction pathways in human breast cancer". Breast Cancer Res. Treat. 27 (1–2): 83–93. PMID 7903175.
- Corfas G, Roy K, Buxbaum JD (2004). "Neuregulin 1-erbB signaling and the molecular/cellular basis of schizophrenia". Nat. Neurosci. 7 (6): 575–80. doi:10.1038/nn1258. PMID 15162166.
- Harrison PJ, Law AJ (2006). "Neuregulin 1 and schizophrenia: genetics, gene expression, and neurobiology". Biol. Psychiatry. 60 (2): 132–40. doi:10.1016/j.biopsych.2005.11.002. PMID 16442083.
- Munafò MR, Thiselton DL, Clark TG, Flint J (2006). "Association of the NRG1 gene and schizophrenia: a meta-analysis". Mol. Psychiatry. 11 (6): 539–46. doi:10.1038/sj.mp.4001817. PMID 16520822.
External links
- Neuregulin-1 at the US National Library of Medicine Medical Subject Headings (MeSH)
- Links from Schizophrenia Research Forum:
- Neuregulin, ErbB4—Levels Normal but Signaling Strengthened in Schizophrenia - 18 June 2006.
- Neuregulin and ErbB4 Mutant Mice Reveal Myelin and Synaptic Deficits - 2 May 2007.
- Functional Neuregulin Variant Linked to Psychosis, Abnormal Brain Activation and IQ - 30 October 2006.
- Neuregulin, ErbB4 Drive Developmental Cell Fates
- Neuregulin Partner ErbB4 Spices Up Genetic Associations - 17 February 2005
- Polymorphisms and Schizophrenia—The Ups and Downs of Neuregulin Expression - 21 April 2006.
- Neuregulin Studies Suggest Synaptic Deficits in Schizophrenia - 4 June 2007