{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:29:47Z","timestamp":1778819387534,"version":"3.51.4"},"reference-count":89,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,14]],"date-time":"2022-01-14T00:00:00Z","timestamp":1642118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971943"],"award-info":[{"award-number":["81971943"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772196"],"award-info":[{"award-number":["81772196"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31470264"],"award-info":[{"award-number":["31470264"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271820"],"award-info":[{"award-number":["81271820"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30870789"],"award-info":[{"award-number":["30870789"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30300117"],"award-info":[{"award-number":["30300117"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012224","name":"Stanley Foundation","doi-asserted-by":"publisher","award":["06R-1366"],"award-info":[{"award-number":["06R-1366"]}],"id":[{"id":"10.13039\/100012224","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007046","name":"Wuhan University","doi-asserted-by":"publisher","award":["TFJC 2018002"],"award-info":[{"award-number":["TFJC 2018002"]}],"id":[{"id":"10.13039\/501100007046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>An increasing number of studies have begun considering human endogenous retroviruses (HERVs) as potential pathogenic phenomena. Our previous research suggests that HERV-W Envelope (HERV-W ENV), a HERV-W family envelope protein, is elevated in schizophrenia patients and contributes to the pathophysiology of schizophrenia. The dopamine (DA) hypothesis is the cornerstone in research and clinical practice related to schizophrenia. Here, we found that the concentration of DA and the expression of DA receptor D2 (DRD2) were significantly higher in schizophrenia patients than in healthy individuals. Intriguingly, there was a positive correlation between HERV-W ENV and DA concentration. Depth analyses showed that there was a marked consistency between HERV-W ENV and DRD2 in schizophrenia. Studies in vitro indicated that HERV-W ENV could increase the DA concentration by regulating DA metabolism and induce the expression of DRD2. Co-IP assays and laser confocal scanning microscopy indicated cellular colocalization and a direct interaction between DRD2 and HERV-W ENV. Additionally, HERV-W ENV caused structural and functional abnormalities of DA neurons. Further studies showed that HERV-W ENV could trigger the PP2A\/AKT1\/GSK3 pathway via DRD2. A whole-cell patch-clamp analysis suggested that HERV-W ENV enhanced sodium influx through DRD2. In conclusion, we uncovered a relationship between HERV-W ENV and the dopaminergic system in the DA neurons. Considering that GNbAC1, a selective monoclonal antibody to the MSRV-specific epitope, has been promised as a therapy for treating type 1 diabetes and multiple sclerosis (MS) in clinical trials, understanding the precise function of HERV-W ENV in the dopaminergic system may provide new insights into the treatment of schizophrenia.<\/jats:p>","DOI":"10.3390\/v14010145","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:46:06Z","timestamp":1642365966000},"page":"145","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2\/PP2A\/AKT1\/GSK3 for Schizophrenia Risk"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9568-6073","authenticated-orcid":false,"given":"Qiujin","family":"Yan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiulin","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuhang","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongchun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huawei","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaru","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7031-2956","authenticated-orcid":false,"given":"Fan","family":"Zhu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy & Immunology, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1146\/annurev-genet-040620-022145","article-title":"A field guide to eukaryotic transposable elements","volume":"54","author":"Wells","year":"2020","journal-title":"Annu Rev. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4892","DOI":"10.1073\/pnas.78.8.4892","article-title":"Identification and cloning of endogenous retroviral sequences present in human DNA","volume":"78","author":"Martin","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/35057062","article-title":"Initial sequencing and analysis of the human genome","volume":"409","author":"Lander","year":"2001","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S1017","DOI":"10.1186\/gb-2001-2-6-reviews1017","article-title":"Endogenous retroviruses in the human genome sequence","volume":"2","author":"Griffiths","year":"2001","journal-title":"Genome Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3947","DOI":"10.1038\/onc.2013.366","article-title":"Mutations in 3\u2032-long terminal repeat of HERV-W family in chromosome 7 upregulate syncytin-1 expression in urothelial cell carcinoma of the bladder through interacting with c-Myb","volume":"33","author":"Yu","year":"2014","journal-title":"Oncogene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1002\/eji.201948423","article-title":"Syncytin-1\/HERV-W envelope is an early activation marker of leukocytes and is upregulated in multiple sclerosis patients","volume":"50","author":"Casanova","year":"2020","journal-title":"Eur. J. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s41420-021-00562-5","article-title":"Implication of human endogenous retrovirus W family envelope in hepatocellular carcinoma promotes MEK\/ERK-mediated metastatic invasiveness and doxorubicin resistance","volume":"7","author":"Zhou","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e94387","DOI":"10.1172\/jci.insight.94387","article-title":"An ancestral retroviral protein identified as a therapeutic target in type-1 diabetes","volume":"2","author":"Levet","year":"2017","journal-title":"JCI Insight"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41398-021-01499-0","article-title":"Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis","volume":"11","author":"Tamouza","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1093\/schbul\/sbp166","article-title":"Implication of the env gene of the human endogenous retrovirus W family in the expression of BDNF and DRD3 and development of recent-onset schizophrenia","volume":"37","author":"Huang","year":"2011","journal-title":"Schizophr. Bull."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.biopsych.2008.06.028","article-title":"Endogenous retrovirus type W GAG and envelope protein antigenemia in serum of schizophrenic patients","volume":"64","author":"Perron","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.bbi.2017.09.009","article-title":"Syncytin-1, an endogenous retroviral protein, triggers the activation of CRP via TLR3 signal cascade in glial cells","volume":"67","author":"Wang","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e201","DOI":"10.1038\/tp.2012.125","article-title":"Molecular characteristics of Human Endogenous Retrovirus type-W in schizophrenia and bipolar disorder","volume":"2","author":"Perron","year":"2012","journal-title":"Transl. Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"c708","DOI":"10.1126\/sciadv.abc0708","article-title":"Human endogenous retroviral protein triggers deficit in glutamate synapse maturation and behaviors associated with psychosis","volume":"6","author":"Johansson","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.5498\/wjp.v11.i11.1075","article-title":"CPEB1, a novel risk gene in recent-onset schizophrenia, contributes to mitochondrial complex I defect caused by a defective provirus ERVWE1","volume":"11","author":"Xia","year":"2021","journal-title":"World J. Psychiatry"},{"key":"ref_16","first-page":"436","article-title":"Prognose der Dementia Praecox (Schizophreniegruppe)","volume":"65","author":"Bleuler","year":"1907","journal-title":"Allg. Z. Psychiat. Psych.-Gerichitliche Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.euroneuro.2005.04.009","article-title":"Size of burden of schizophrenia and psychotic disorders","volume":"15","author":"Rossler","year":"2005","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Stepnicki, P., Kondej, M., and Kaczor, A.A. (2018). Current concepts and treatments of schizophrenia. Molecules, 23.","DOI":"10.3390\/molecules23082087"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1093\/schbul\/sbp006","article-title":"The dopamine hypothesis of schizophrenia: Version III\u2014The final common pathway","volume":"35","author":"Howes","year":"2009","journal-title":"Schizophr. Bull."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.cell.2005.05.012","article-title":"An Akt\/beta-arrestin 2\/PP2A signaling complex mediates dopaminergic neurotransmission and behavior","volume":"122","author":"Beaulieu","year":"2005","journal-title":"Cell"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1093\/bib\/bbz049","article-title":"Consistent gene signature of schizophrenia identified by a novel feature selection strategy from comprehensive sets of transcriptomic data","volume":"21","author":"Yang","year":"2020","journal-title":"Brief. Bioinform."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ng1296","article-title":"Convergent evidence for impaired AKT1-GSK3\u03b2 signaling in schizophrenia","volume":"36","author":"Emamian","year":"2004","journal-title":"Nat. Genet."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fphar.2020.00344","article-title":"Ribosomal protein s6 hypofunction in postmortem human brain links mTORC1-Dependent signaling and schizophrenia","volume":"11","author":"Morentin","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1016\/j.tips.2010.05.004","article-title":"Signaling pathways in schizophrenia: Emerging targets and therapeutic strategies","volume":"31","author":"Karam","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"30144","DOI":"10.3390\/ijms161226228","article-title":"Alterations of dopamine d2 receptors and related Receptor-Interacting proteins in schizophrenia: The pivotal position of dopamine supersensitivity psychosis in Treatment-Resistant schizophrenia","volume":"16","author":"Oda","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1002\/jnr.22647","article-title":"Transcription and pathway analysis of the superior temporal cortex and anterior prefrontal cortex in schizophrenia","volume":"89","author":"Barnes","year":"2011","journal-title":"J. Neurosci. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1093\/bioinformatics\/btm254","article-title":"GEOquery: A bridge between the Gene Expression Omnibus (GEO) and BioConductor","volume":"23","author":"Davis","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic. Acids Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/nature09915","article-title":"Modelling schizophrenia using human induced pluripotent stem cells","volume":"473","author":"Brennand","year":"2011","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/0306-4522(93)90342-D","article-title":"Midbrain dopaminergic neurons from postnatal rat in long-term primary culture","volume":"56","author":"Cardozo","year":"1993","journal-title":"Neuroscience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"12748","DOI":"10.1073\/pnas.171442798","article-title":"Visualizing recycling synaptic vesicles in hippocampal neurons by FM 1-43 photoconversion","volume":"98","author":"Harata","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1364\/BOE.4.002644","article-title":"Re-scan confocal microscopy: Scanning twice for better resolution. Biomed","volume":"4","author":"Breedijk","year":"2013","journal-title":"Opt. Express."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11174","DOI":"10.1074\/jbc.M111.309070","article-title":"Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A)","volume":"287","author":"Sun","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1016\/S0006-3495(03)74642-6","article-title":"Spontaneous activity of dopaminergic retinal neurons","volume":"85","author":"Steffen","year":"2003","journal-title":"Biophys. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.7150\/jca.27780","article-title":"The Prospective Value of Dopamine Receptors on Bio-Behavior of Tumor","volume":"10","author":"Wang","year":"2019","journal-title":"J. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1038\/mp.2011.20","article-title":"Progressive increase in striatal dopamine synthesis capacity as patients develop psychosis: A PET study","volume":"16","author":"Howes","year":"2011","journal-title":"Mol. Psychiatry"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26677","DOI":"10.3390\/ijms161125983","article-title":"The mRNA expression status of dopamine receptor d2, dopamine receptor d3 and DARPP-32 in T lymphocytes of patients with early psychosis","volume":"16","author":"Cui","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, L., Yuan, G., Cheng, Z., Zhang, G., Liu, X., and Zhang, H. (2013). Identification of the mRNA expression status of the dopamine D2 receptor and dopamine transporter in peripheral blood lymphocytes of schizophrenia patients. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075259"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.jpsychires.2007.07.011","article-title":"Verification of proposed peripheral biomarkers in mononuclear cells of individuals with schizophrenia","volume":"42","author":"Yao","year":"2008","journal-title":"J. Psychiatry Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y cell line in Parkinson\u2019s disease research: A systematic review","volume":"12","author":"Xicoy","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1111\/jnc.15034","article-title":"Direct dopamine terminal regulation by local striatal microcircuitry","volume":"155","author":"Nolan","year":"2020","journal-title":"J. Neurochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"248","DOI":"10.3389\/fncel.2020.00248","article-title":"Commentary: Ghrelin promotes midbrain neural stem cells differentiation to dopaminergic neurons through the Wnt\/beta-catenin pathway","volume":"14","author":"Gayden","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.tips.2013.07.005","article-title":"Mechanisms of dopamine transporter regulation in normal and disease states","volume":"34","author":"Vaughan","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1085\/jgp.201711980","article-title":"The ins and outs of vesicular monoamine transporters","volume":"150","author":"Yaffe","year":"2018","journal-title":"J. Gen. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"109669","DOI":"10.1016\/j.pnpbp.2019.109669","article-title":"Differential expression of synaptic markers regulated during neurodevelopment in a rat model of schizophrenia-like behavior","volume":"95","author":"Elfving","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1091\/mbc.e04-07-0559","article-title":"Normal biogenesis and cycling of empty synaptic vesicles in dopamine neurons of vesicular monoamine transporter 2 knockout mice","volume":"16","author":"Croft","year":"2005","journal-title":"Mol. Biol. Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.1523\/JNEUROSCI.2970-04.2005","article-title":"Early presynaptic and late postsynaptic components contribute independently to brain-derived neurotrophic factor-induced synaptic plasticity","volume":"25","author":"Alder","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rotter, A., Lenz, B., Pitsch, R., Richter-Schmidinger, T., Kornhuber, J., and Rhein, C. (2019). Alpha-Synuclein RNA expression is increased in major depression. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20082029"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev.cellbio.16.1.19","article-title":"Mechanisms of synaptic vesicle exocytosis","volume":"16","author":"Lin","year":"2000","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1111\/jpi.12114","article-title":"Melatonin improves neuroplasticity by upregulating the growth-associated protein-43 (GAP-43) and NMDAR postsynaptic density-95 (PSD-95) proteins in cultured neurons exposed to glutamate excitotoxicity and in rats subjected to transient focal cerebral ischemia even during a long-term recovery period","volume":"56","author":"Juan","year":"2014","journal-title":"J. Pineal. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1126\/science.290.5492.750","article-title":"Signal-processing machines at the postsynaptic density","volume":"290","author":"Kennedy","year":"2000","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5187","DOI":"10.1073\/pnas.0611619104","article-title":"Dopamine modulation of neuronal Na(+) channels requires binding of a kinase-anchoring protein 15 and PKA by a modified leucine zipper motif","volume":"104","author":"Few","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","first-page":"317","article-title":"Biophysical properties of somatic and axonal Voltage-Gated sodium channels in midbrain dopaminergic neurons","volume":"13","author":"Yang","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"5248","DOI":"10.1038\/s41598-017-05578-5","article-title":"Calcium-activated SK channels control firing regularity by modulating sodium channel availability in midbrain dopamine neurons","volume":"7","author":"Iyer","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1073\/pnas.0305763101","article-title":"The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology","volume":"101","author":"Mallet","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"422","DOI":"10.3389\/fpsyt.2018.00422","article-title":"Human endogenous retroviral envelope protein syncytin-1 and inflammatory abnormalities in neuropsychological diseases","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12250-017-3984-9","article-title":"Human leukemia antigen-A*0201-restricted epitopes of human endogenous retrovirus W family envelope (HERV-W env) induce strong cytotoxic T lymphocyte responses","volume":"32","author":"Tu","year":"2017","journal-title":"Virol. Sin."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1007\/s00705-020-04933-8","article-title":"Human endogenous retrovirus W family envelope protein (HERV-W env) facilitates the production of TNF-alpha and IL-10 by inhibiting MyD88s in glial cells","volume":"166","author":"Wang","year":"2021","journal-title":"Arch. Virol"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1007\/s12250-017-3997-4","article-title":"Human endogenous retrovirus W env increases nitric oxide production and enhances the migration ability of microglia by regulating the expression of inducible nitric oxide synthase","volume":"32","author":"Xiao","year":"2017","journal-title":"Virol. Sin."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.biopsych.2013.11.023","article-title":"Selective overexpression of dopamine D3 receptors in the striatum disrupts motivation but not cognition","volume":"76","author":"Simpson","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4832","DOI":"10.1096\/fj.201900577RRRR","article-title":"Cell adhesion molecule close homolog of L1 binds to the dopamine receptor D2 and inhibits the internalization of its short isoform","volume":"34","author":"Kotarska","year":"2020","journal-title":"FASEB J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1080\/14728222.2017.1272581","article-title":"Tyrosine and tryptophan hydroxylases as therapeutic targets in human disease","volume":"21","author":"Waloen","year":"2017","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bosiacki, M., Gassowska-Dobrowolska, M., Kojder, K., Fabianska, M., Jezewski, D., Gutowska, I., and Lubkowska, A. (2019). Perineuronal nets and their role in synaptic homeostasis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20174108"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/bies.20012","article-title":"Synaptophysin: Leading actor or walk-on role in synaptic vesicle exocytosis?","volume":"26","author":"Valtorta","year":"2004","journal-title":"Bioessays"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1146\/annurev.neuro.26.041002.131412","article-title":"The synaptic vesicle cycle","volume":"27","author":"Sudhof","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s00702-008-0149-x","article-title":"Aging and alpha-synuclein affect synaptic plasticity in the dentate gyrus","volume":"116","author":"Gureviciene","year":"2009","journal-title":"J. Neural. Transm."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.parkreldis.2016.01.028","article-title":"Schizophrenia as a prodromal symptom in a patient harboring SNCA duplication","volume":"25","author":"Takamura","year":"2016","journal-title":"Parkinsonism. Relat. Disord."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1385\/JMN:13:1-2:101","article-title":"The growth-associated protein GAP-43 is increased in the hippocampus and in the gyrus cinguli in schizophrenia","volume":"13","author":"Blennow","year":"1999","journal-title":"J. Mol. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1126\/science.1155174","article-title":"Rare structural variants disrupt multiple genes in neurodevelopmental pathways in schizophrenia","volume":"320","author":"Walsh","year":"2008","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bbr.2016.08.054","article-title":"Association of functional genetic variation in PP2A with prefrontal working memory processing","volume":"316","author":"Rampino","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"298","DOI":"10.3389\/fncel.2019.00298","article-title":"Astrocytic Insulin-Like growth factor-1 protects neurons against excitotoxicity","volume":"13","author":"Chen","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41419-018-0309-3","article-title":"Glycogen synthase kinase-3beta inhibition promotes lysosome-dependent degradation of c-FLIPL in hepatocellular carcinoma","volume":"9","author":"Zhang","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5616","DOI":"10.1167\/iovs.14-14371","article-title":"The mitochondrial complex I inhibitor rotenone induces endoplasmic reticulum stress and activation of GSK-3beta in cultured rat retinal cells","volume":"55","author":"Han","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"6050","DOI":"10.1007\/s12035-017-0823-9","article-title":"GSK3beta controls mTOR and prosurvival signaling in neurons","volume":"55","author":"Urbanska","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.neulet.2016.05.036","article-title":"Elevation of Ser9 phosphorylation of GSK3beta is required for HERV-W env-mediated BDNF signaling in human U251 cells","volume":"627","author":"Qin","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s13365-018-0692-7","article-title":"HERV-W env regulates calcium influx via activating TRPC3 channel together with depressing DISC1 in human neuroblastoma cells","volume":"25","author":"Chen","year":"2019","journal-title":"J. Neurovirol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.neuroscience.2013.05.033","article-title":"Human endogenous retrovirus W family envelope gene activates the small conductance Ca2+-activated K+ channel in human neuroblastoma cells through CREB","volume":"247","author":"Li","year":"2013","journal-title":"Neuroscience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"10163","DOI":"10.1523\/JNEUROSCI.22-23-10163.2002","article-title":"Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding","volume":"22","author":"Stackman","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nrn2870","article-title":"GSK3 signalling in neural development","volume":"11","author":"Hur","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/s41593-020-00780-7","article-title":"Phagocyte-mediated synapse removal in cortical neuroinflammation is promoted by local calcium accumulation","volume":"24","author":"Jafari","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1159\/000095115","article-title":"Differentiated dopaminergic MN9D cells only partially recapitulate the electrophysiological properties of midbrain dopaminergic neurons","volume":"28","author":"Rick","year":"2006","journal-title":"Dev. Neurosci."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1097\/YPG.0000000000000110","article-title":"Mutation screening of SCN2A in schizophrenia and identification of a novel loss-of-function mutation","volume":"26","author":"Carroll","year":"2016","journal-title":"Psychiatr. Genet."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/glia.23535","article-title":"Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination","volume":"67","author":"Gottle","year":"2019","journal-title":"Glia"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1111\/dom.13357","article-title":"A new therapeutic approach for type 1 diabetes: Rationale for GNbAC1, an anti-HERV-W-Env monoclonal antibody","volume":"20","author":"Curtin","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Hartung, H.P., Derfuss, T., Cree, B.A., Sormani, M.P., Selmaj, K., Stutters, J., Prados, F., MacManus, D., Schneble, H.M., and Lambert, E. (2021). Efficacy and safety of temelimab in multiple sclerosis: Results of a randomized phase 2b and extension study. Mult. Scler., 516106651.","DOI":"10.1177\/13524585211024997"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1278055142","DOI":"10.1177\/1756286419833574","article-title":"The monoclonal antibody GNbAC1, Targeting human endogenous retroviruses in multiple sclerosis","volume":"12","author":"Diebold","year":"2019","journal-title":"Ther. Adv. Neurol. Disord."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1016\/j.clinthera.2012.11.006","article-title":"GNbAC1, a humanized monoclonal antibody against the envelope protein of multiple sclerosis-associated endogenous retrovirus: A first-in-humans randomized clinical study","volume":"34","author":"Curtin","year":"2012","journal-title":"Clin. Ther."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/1\/145\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:15:01Z","timestamp":1760364901000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/1\/145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,14]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["v14010145"],"URL":"https:\/\/doi.org\/10.3390\/v14010145","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,14]]}}}