000136519 001__ 136519 000136519 005__ 20240321220102.0 000136519 0247_ $$2doi$$a10.2174/156720512799361637 000136519 0247_ $$2pmid$$apmid:22455478 000136519 0247_ $$2ISSN$$a1567-2050 000136519 0247_ $$2ISSN$$a1875-5828 000136519 0247_ $$2altmetric$$aaltmetric:42826406 000136519 037__ $$aDZNE-2020-02841 000136519 041__ $$aEnglish 000136519 082__ $$a610 000136519 1001_ $$0P:(DE-2719)9000073$$aFleck, Daniel$$b0$$eFirst author$$udzne 000136519 245__ $$aBACE1 dependent neuregulin processing: review. 000136519 260__ $$aHilversum$$bBentham Science Publ. Ltd.$$c2012 000136519 264_1 $$2Crossref$$3print$$bBentham Science Publishers Ltd.$$c2012-02-01 000136519 3367_ $$2DRIVER$$aarticle 000136519 3367_ $$2DataCite$$aOutput Types/Journal article 000136519 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1589540111_30801$$xReview Article 000136519 3367_ $$2BibTeX$$aARTICLE 000136519 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000136519 3367_ $$00$$2EndNote$$aJournal Article 000136519 520__ $$aNeuregulin-1 (NRG1), known also as heregulin, acetylcholine receptor inducing activity (ARIA), glial growth factor (GGF), or sensory and motor neuron derived factor (SMDF), plays essential roles in several developmental processes, and is required also later in life. Many variants of NRG1 are produced via alternative splicing and usage of distinct promoters. All contain an epidermal growth factor (EGF)-like domain, which alone is sufficient to bind and activate the cognate receptors, members of the ErbB family. NRG1 mediated signaling is crucial for cardiogenesis and the development of the mammary gland and ErbB2 (HER2), an orphan co-receptor for NRG1 is the target of the drug Herceptin� (trastuzumab) used for treatment of metastatic breast cancer. In the nervous system, NRG1 controls the early development of subpopulations of neural crest cells. In particular, NRG1 acts as an essential paracrine signaling molecule expressed on the axonal surface, where it signals to Schwann cells throughout development and regulates the thickness of the myelin sheath. NRG1 is required also by other cell types in the nervous system, for instance as an axonal signal released by proprioceptive afferents to induce development of the muscle spindle, and it controls aspects of cortical interneuron development as well as the formation of thalamocortical projections. Work from several laboratories implicates dysregulation of NRG1/ErbB4 signaling in the etiology of schizophrenia. Biochemical studies have shown that the precursor proteins of NRG1 can be released from the membrane through limited proteolysis. In addition, most NRG1 isoforms contain a transmembrane domain, which is processed by γ-secretase after shedding. Thereby the intracellular domain is released into the cytoplasm. Despite this, the importance of NRG1 cleavage for its functions in vivo remained unclear until recently. β- Secretase (β-site amyloid precursor protein cleaving enzyme 1, BACE1) was first identified through its function as the rate limiting enzyme of amyloid-β-peptide (Aβ) production. Aβ is the major component of amyloid plaques in Alzheimer's disease (AD). More recently it was shown that Neuregulin-1 is a major physiological substrate of BACE1 during early postnatal development. Mutant mice lacking BACE1 display severe hypomyelination of peripheral nerves similar to that seen in mice lacking NRG1/ErbB signaling in Schwann cells, and a BACE1-dependent activation of NRG1 in the process of peripheral myelination was proposed. Here we summarize the current knowledge about the role of NRG1 proteolysis for ErbB receptor mediated signaling during development and in Alzheimer's disease. 000136519 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0 000136519 588__ $$aDataset connected to CrossRef, PubMed, 000136519 650_7 $$2NLM Chemicals$$aNeuregulins 000136519 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aEGFR protein, human 000136519 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aErbB Receptors 000136519 650_7 $$0EC 3.4.-$$2NLM Chemicals$$aAmyloid Precursor Protein Secretases 000136519 650_7 $$0EC 3.4.23.-$$2NLM Chemicals$$aAspartic Acid Endopeptidases 000136519 650_7 $$0EC 3.4.23.46$$2NLM Chemicals$$aBACE1 protein, human 000136519 650_2 $$2MeSH$$aAmyloid Precursor Protein Secretases: metabolism 000136519 650_2 $$2MeSH$$aAnimals 000136519 650_2 $$2MeSH$$aAspartic Acid Endopeptidases: metabolism 000136519 650_2 $$2MeSH$$aErbB Receptors: metabolism 000136519 650_2 $$2MeSH$$aHumans 000136519 650_2 $$2MeSH$$aMice 000136519 650_2 $$2MeSH$$aModels, Biological 000136519 650_2 $$2MeSH$$aNeuregulins: genetics 000136519 650_2 $$2MeSH$$aNeuregulins: metabolism 000136519 650_2 $$2MeSH$$aSignal Transduction: physiology 000136519 7001_ $$aGarratt, Alistair N$$b1 000136519 7001_ $$0P:(DE-2719)2202037$$aHaass, Christian$$b2$$udzne 000136519 7001_ $$0P:(DE-2719)9000433$$aWillem, Michael$$b3$$eLast author$$udzne 000136519 77318 $$2Crossref$$3journal-article$$a10.2174/156720512799361637$$b : Bentham Science Publishers Ltd., 2012-02-01$$n2$$p178-183$$tCurrent Alzheimer Research$$v9$$x1567-2050$$y2012 000136519 773__ $$0PERI:(DE-600)2155964-8$$a10.2174/156720512799361637$$gVol. 9, no. 2, p. 178 - 183$$n2$$p178-183$$q9:2<178 - 183$$tCurrent Alzheimer research$$v9$$x1567-2050$$y2012 000136519 909CO $$ooai:pub.dzne.de:136519$$pVDB 000136519 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000073$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b0$$kDZNE 000136519 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2202037$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b2$$kDZNE 000136519 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)9000433$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b3$$kDZNE 000136519 9131_ $$0G:(DE-HGF)POF3-342$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$aDE-HGF$$bForschungsbereich Gesundheit$$lErkrankungen des Nervensystems$$vDisease Mechanisms and Model Systems$$x0 000136519 9141_ $$y2012 000136519 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000136519 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000136519 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bCURR ALZHEIMER RES : 2017 000136519 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000136519 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000136519 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000136519 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000136519 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews 000136519 915__ $$0StatID:(DE-HGF)1120$$2StatID$$aDBCoverage$$bBIOSIS Reviews Reports And Meetings 000136519 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5 000136519 9201_ $$0I:(DE-2719)1110007$$kAG Haass old$$lALS, FTLD and Zebrafish models$$x0 000136519 9201_ $$0I:(DE-2719)5000048$$kExt LMU$$lExt Ludwig-Maximilians-University$$x1 000136519 980__ $$ajournal 000136519 980__ $$aVDB 000136519 980__ $$aI:(DE-2719)5000015 000136519 980__ $$aI:(DE-2719)5000048 000136519 980__ $$aUNRESTRICTED