{"doi":"10.3389/fnmol.2017.00302","title":"BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia","abstract":null,"journal":"Frontiers in Molecular Neuroscience","year":2017,"id":647247,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":14808,"name":"Jing Huang","orcid":"0000-0001-7116-5847","position":1,"is_corresponding":false},{"id":664504,"name":"Yong Shen","orcid":"0000-0002-1232-7970","position":2,"is_corresponding":false},{"id":928663,"name":"Rena Li","orcid":"0000-0001-9729-9472","position":3,"is_corresponding":false},{"id":493567,"name":"Zhengrong Zhang","orcid":"0000-0002-0608-8520","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia","abstract":"Schizophrenia is a chronic psychiatric disorder with a lifetime prevalence of about 1% in the general population. Recent studies have shown that Neuregulin-1 (Nrg1) is a candidate gene for schizophrenia. At least 15 alternative splicing of NRG1 isoforms all contain an extracellular epidermal growth factor (EGF)-like domain, which is sufficient for Nrg1 biological activity including the formation of myelin sheaths and the regulation of synaptic plasticity. It is known that Nrg1 can be cleaved by β-secretase (BACE1) and the resulting N-terminal fragment (Nrg1-ntf) binds to receptor tyrosine kinase ErbB4, which activates Nrg1/ErbB4 signaling. While changes in Nrg1 expression levels in schizophrenia still remain controversial, understanding the BACE1-cleaved Nrg1-ntf and Nrg1/ErbB4 signaling in schizophrenia neuropathogenesis is essential and important. In this review paper, we included three major parts: (1) Nrg1 structure and cleavage pattern by BACE1; (2) BACE1-dependent Nrg1 cleavage associated with schizophrenia in human studies; and (3) Animal studies of Nrg1 and BACE1 mutations with behavioral observations. Our review will provide a better understanding of Nrg1 in schizophrenia and a potential strategy for using BACE1 cleavage of Nrg1 as a unique biomarker for diagnosis, as well as a new therapeutic target, of schizophrenia.","is_dataset_classified":null,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28993723","pmcid":"PMC5622153","openalex_id":"https://openalex.org/W2759755712","authors":[],"funders":[{"funder_name":"NIA NIH HHS","grant_id":"R21 AG049237","title":null},{"funder_name":"NIA NIH HHS","grant_id":"R01 AG032441","title":null},{"funder_name":"NINDS NIH HHS","grant_id":"R01 NS092610","title":null},{"funder_name":"National Institutes of Health","grant_id":"1R01NS092610-01A1","title":"PATHOBIOLOGICAL STUDIES OF VESSEL BACE1 IN CEREBROVASCULAR AMYLOID ANGIOPATHY"},{"funder_name":"National Institutes of Health","grant_id":"1R21AG049237-01A1","title":"Proteomic Studies of Protein Pathways for the Estrogen Therapeutic Window in AD"}],"total_grants":5,"fwci":0.8598,"citation_percentile":0.74941414,"influential_citations":0,"citation_trend":[{"year":2018,"count":1},{"year":2019,"count":1},{"year":2020,"count":6},{"year":2021,"count":3},{"year":2022,"count":4},{"year":2023,"count":6},{"year":2024,"count":5},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fnmol.2017.00302/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fnmol.2017.00302/pdf","host_type":"publisher"},{"url":"http://journal.frontiersin.org/article/10.3389/fnmol.2017.00302/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fnmol.2017.00302","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28993723","host_type":"repository"},{"url":"https://doaj.org/article/1d991296405d49aa80fa17dde912e865","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5622153","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5622153","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5622153?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3389/fnmol.2017.00302","host_type":""},{"url":"https://dx.doi.org/10.3389/fnmol.2017.00302","host_type":""}],"fields_of_study":["HER2/EGFR in Cancer Research","14-3-3 protein interactions","Cytokine Signaling Pathways and Interactions","0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":[],"keywords":["Neuregulin 1","ERBB4","ErbB","Neuregulin","Schizophrenia (object-oriented programming)","Neuroscience","Alternative splicing","Tyrosine kinase","Receptor tyrosine kinase","Signal transduction","Gene isoform","Biology","Medicine","Cell biology","Gene","Genetics","Psychiatry","Schizophrenia","Signaling pathway","Β-secretase (Bace1)","Neuregulin-1 (Nrg1)","Erb-b2 Receptor Tyrosine Kinase 4 (Erbb4)","Neurosciences. 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