{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T06:09:04Z","timestamp":1771308544186,"version":"3.50.1"},"reference-count":83,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T00:00:00Z","timestamp":1771027200000},"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":"crossref","award":["82272321"],"award-info":[{"award-number":["82272321"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Stanley Foundation from the Stanley Medical Research Institute (SMRI), United States","award":["06R-1366"],"award-info":[{"award-number":["06R-1366"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Schizophrenia is a severe neurodevelopmental disorder with a complex and largely unresolved pathogenesis. Accumulating evidence indicates that mitochondrial dysfunction is a consistent pathological hallmark of schizophrenia, suggesting that impaired mitochondrial homeostasis may represent a convergent mechanism underlying disease vulnerability. BCL2\/adenovirus E1B 19 kDa interacting protein 3 (BNIP3) is a critical regulator of mitochondrial integrity and apoptosis. However, its role in schizophrenia has not yet been elucidated. Human endogenous retroviruses W family envelope (ERVWE1) has been implicated as a potential risk factor in schizophrenia, but the molecular mechanisms by which it contributes to neuronal pathology remain poorly understood. In this study, we investigated whether ERVWE1 induces mitochondrial dysfunction and neuronal apoptosis through the regulation of BNIP3. Bioinformatic analysis of the public dataset GSE53987 revealed significantly elevated BNIP3 expression in the brain tissues of patients with schizophrenia, accompanied by enrichment of mitochondria-related pathways. Consistently, BNIP3 expression was also increased in the peripheral blood of schizophrenia patients and positively correlated with ERVWE1 levels. Mechanistically, ERVWE1 upregulated BNIP3 expression by suppressing miR-27b-3p, a microRNA that directly targets BNIP3. The resulting increase in BNIP3 led to marked mitochondrial structural and functional impairment, characterized by reduced mitochondrial aspect ratio, enhanced mitochondria permeability transition pore (mPTP) opening, and decreased mitochondrial DNA (mtDNA) copy number. These mitochondrial defects subsequently triggered cytochrome c release into the cytosol, activating the intrinsic mitochondrial apoptotic pathway. Collectively, this study provides the first evidence that the ERVWE1\/miR-27b-3p\/BNIP3 axis contributes to mitochondrial dysfunction and neuronal apoptosis in schizophrenia. Our findings identify a previously unrecognized molecular pathway linking endogenous retroviral activity to mitochondrial pathology, offering novel insights into the mechanisms and potential therapeutic targets for schizophrenia.<\/jats:p>","DOI":"10.3390\/v18020245","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T11:11:28Z","timestamp":1771240288000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ERVWE1 Impairs Mitochondrial Homeostasis and Promotes Neuronal Apoptosis via the miR-27b-3p\/BNIP3 Axis in Schizophrenia"],"prefix":"10.3390","volume":"18","author":[{"given":"Yaru","family":"Su","sequence":"first","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kexin","family":"Zhao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahang","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Lv","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyi","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology and Biosafety, 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 and Biosafety, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"},{"name":"Hubei Province Key Laboratory of Allergy and Immunology, Department of Medical Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1093\/schbul\/sby058","article-title":"Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study 2016","volume":"44","author":"Charlson","year":"2018","journal-title":"Schizophr. Bull."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1038\/mp.2012.23","article-title":"Neurodevelopmental model of schizophrenia: Update 2012","volume":"17","author":"Rapoport","year":"2012","journal-title":"Mol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1038\/s41380-021-01316-6","article-title":"Schizophrenia is defined by cell-specific neuropathology and multiple neurodevelopmental mechanisms in patient-derived cerebral organoids","volume":"27","author":"Notaras","year":"2022","journal-title":"Mol. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.schres.2008.01.022","article-title":"Schizophrenia, \u201cJust the Facts\u201d: What we know in 2008 part 1: Overview","volume":"100","author":"Tandon","year":"2008","journal-title":"Schizophr. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41467-023-36649-z","article-title":"Endogenous retroviruses and TDP-43 proteinopathy form a sustaining feedback driving intercellular spread of Drosophila neurodegeneration","volume":"14","author":"Chang","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0006-3223(01)01068-X","article-title":"Prenatal rubella, premorbid abnormalities, and adult schizophrenia","volume":"49","author":"Brown","year":"2001","journal-title":"Biol. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.biopsych.2007.09.022","article-title":"Maternal exposure to herpes simplex virus and risk of psychosis among adult offspring","volume":"63","author":"Buka","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1001\/archpsyc.61.8.774","article-title":"Serologic evidence of prenatal influenza in the etiology of schizophrenia","volume":"61","author":"Brown","year":"2004","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/35001608","article-title":"Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis","volume":"403","author":"Mi","year":"2000","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1176\/appi.neuropsych.15030059","article-title":"Pathophysiological Role of HERV-W in Schizophrenia","volume":"28","author":"Aftab","year":"2016","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1126\/science.283.5407.1482","article-title":"Mitochondrial diseases in man and mouse","volume":"283","author":"Wallace","year":"1999","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/s41398-022-02127-1","article-title":"Mitochondria DNA copy number, mitochondria DNA total somatic deletions, Complex I activity, synapse number, and synaptic mitochondria number are altered in schizophrenia and bipolar disorder","volume":"12","author":"Das","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, X., Huang, J., and Zhu, F. (2018). Human Endogenous Retroviral Envelope Protein Syncytin-1 and Inflammatory Abnormalities in Neuropsychological Diseases. Front. Psychiatry, 9.","DOI":"10.3389\/fpsyt.2018.00422"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.virs.2025.05.007","article-title":"Human endogenous retrovirus W family envelope protein (ERVWE1) regulates macroautophagy activation and micromitophagy inhibition via NOXA1 in schizophrenia","volume":"40","author":"Zhang","year":"2025","journal-title":"Virol. Sin."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1016\/j.neuron.2008.10.010","article-title":"Mitochondria in neuroplasticity and neurological disorders","volume":"60","author":"Mattson","year":"2008","journal-title":"Neuron"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1089\/ars.2010.3386","article-title":"Neuronal calcium homeostasis and dysregulation","volume":"14","author":"Gleichmann","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/j.1460-9568.2010.07345.x","article-title":"Mitochondrial trafficking and the provision of energy and calcium buffering at excitatory synapses","volume":"32","author":"MacAskill","year":"2010","journal-title":"Eur. J. Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1089\/ars.2010.3208","article-title":"Reactive oxygen species in the regulation of synaptic plasticity and memory","volume":"14","author":"Massaad","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/07853890801923753","article-title":"Mitochondrial involvement in psychiatric disorders","volume":"40","author":"Shao","year":"2008","journal-title":"Ann. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s12265-010-9174-x","article-title":"Mitochondrial pruning by Nix and BNip3: An essential function for cardiac-expressed death factors","volume":"3","author":"Dorn","year":"2010","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1084\/jem.186.12.1975","article-title":"The E1B 19K\/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis","volume":"186","author":"Chen","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12415","DOI":"10.1074\/jbc.273.20.12415","article-title":"Adenovirus E1B-19K\/BCL-2 interacting protein BNIP3 contains a BH3 domain and a mitochondrial targeting sequence","volume":"273","author":"Yasuda","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4286","DOI":"10.1158\/0008-5472.CAN-03-3084","article-title":"Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells","volume":"64","author":"Daido","year":"2004","journal-title":"Cancer Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1006\/abbi.2001.2673","article-title":"The carboxy terminal C-tail of BNip3 is crucial in induction of mitochondrial permeability transition in isolated mitochondria","volume":"398","author":"Kim","year":"2002","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41398-024-02767-5","article-title":"Autophagy-related gene model as a novel risk factor for schizophrenia","volume":"14","author":"Tan","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4734","DOI":"10.1038\/sj.onc.1206666","article-title":"BNIP3 plays a role in hypoxic cell death in human epithelial cells that is inhibited by growth factors EGF and IGF","volume":"22","author":"Kothari","year":"2003","journal-title":"Oncogene"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1158\/0008-5472.CAN-09-3718","article-title":"MicroRNA145 targets BNIP3 and suppresses prostate cancer progression","volume":"70","author":"Chen","year":"2010","journal-title":"Cancer Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1161\/CIRCRESAHA.118.312758","article-title":"Transplanted Mesenchymal Stem Cells Reduce Autophagic Flux in Infarcted Hearts via the Exosomal Transfer of miR-125b","volume":"123","author":"Xiao","year":"2018","journal-title":"Circ. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12024","DOI":"10.1002\/jev2.12024","article-title":"Adipose-derived mesenchymal stem cells reduce autophagy in stroke mice by extracellular vesicle transfer of miR-25","volume":"10","author":"Kuang","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1080\/15548627.2024.2395799","article-title":"Mir221- and Mir222-enriched adsc-exosomes mitigate PM exposure-exacerbated cardiac ischemia-reperfusion injury through the modulation of the BNIP3-MAP1LC3B-BBC3\/PUMA pathway","volume":"21","author":"Lee","year":"2025","journal-title":"Autophagy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1126\/science.1064921","article-title":"Identification of novel genes coding for small expressed RNAs","volume":"294","author":"Rauhut","year":"2001","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1093\/hmg\/ddn005","article-title":"Dysregulation of miRNA 181b in the temporal cortex in schizophrenia","volume":"17","author":"Beveridge","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.biopsych.2010.09.030","article-title":"Upregulation of dicer and microRNA expression in the dorsolateral prefrontal cortex Brodmann area 46 in schizophrenia","volume":"69","author":"Santarelli","year":"2011","journal-title":"Biol. Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/s43587-024-00802-0","article-title":"Ginkgolide B increases healthspan and lifespan of female mice","volume":"5","author":"Lee","year":"2025","journal-title":"Nat. Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00018-011-0788-1","article-title":"MicroRNA networks direct neuronal development and plasticity","volume":"69","author":"Kos","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/syn.890010203","article-title":"Dopamine receptors and the dopamine hypothesis of schizophrenia","volume":"1","author":"Seeman","year":"1987","journal-title":"Synapse"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.schres.2006.01.007","article-title":"Human endogenous retroviral pol RNA and protein detected and identified in the blood of individuals with schizophrenia","volume":"83","author":"Huang","year":"2006","journal-title":"Schizophr. Res."},{"key":"ref_40","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_41","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1126\/science.abj6987","article-title":"The complete sequence of a human genome","volume":"376","author":"Nurk","year":"2022","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41580-023-00674-z","article-title":"Activation of human endogenous retroviruses and its physiological consequences","volume":"25","author":"Dopkins","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","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_44","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_45","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.biopsych.2006.05.024","article-title":"Toxoplasma gondii as a risk factor for early-onset schizophrenia: Analysis of filter paper blood samples obtained at birth","volume":"61","author":"Mortensen","year":"2007","journal-title":"Biol. Psychiatry"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Jia, C., Zhang, M., Wu, X., Zhang, X., Lv, Z., Zhao, K., Zhang, J., Su, Y., and Zhu, F. (2025). HERV-W Env Induces Neuron Pyroptosis via the NLRP3-CASP1-GSDMD Pathway in Recent-Onset Schizophrenia. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26020520"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8514","DOI":"10.1073\/pnas.1432609100","article-title":"Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway","volume":"100","author":"Lehnardt","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s11262-013-0939-6","article-title":"Activation of elements in HERV-W family by caffeine and aspirin","volume":"47","author":"Liu","year":"2013","journal-title":"Virus Genes"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ibneur.2024.01.007","article-title":"Hub genes, a diagnostic model, and immune infiltration based on ferroptosis-linked genes in schizophrenia","volume":"16","author":"Lian","year":"2024","journal-title":"IBRO Neurosci. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s13578-024-01318-1","article-title":"Ancestral retrovirus envelope protein ERVWE1 upregulates circ_0001810, a potential biomarker for schizophrenia, and induces neuronal mitochondrial dysfunction via activating AK2","volume":"14","author":"Li","year":"2024","journal-title":"Cell Biosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.neulet.2016.05.036","article-title":"Elevation of Ser9 phosphorylation of GSK3\u03b2 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_52","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_53","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.virs.2022.08.005","article-title":"Domesticated HERV-W env contributes to the activation of the small conductance Ca2+-activated K+ type 2 channels via decreased 5-HT4 receptor in recent-onset schizophrenia","volume":"38","author":"Wu","year":"2023","journal-title":"Virol. Sin."},{"key":"ref_54","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_55","doi-asserted-by":"crossref","unstructured":"Yan, Q., Wu, X., Zhou, P., Zhou, Y., Li, X., Liu, Z., Tan, H., Yao, W., Xia, Y., and Zhu, F. (2022). HERV-W Envelope Triggers Abnormal Dopaminergic Neuron Process through DRD2\/PP2A\/AKT1\/GSK3 for Schizophrenia Risk. Viruses, 14.","DOI":"10.3390\/v14010145"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Xue, X., Wu, X., Liu, L., Liu, L., and Zhu, F. (2023). ERVW-1 Activates ATF6-Mediated Unfolded Protein Response by Decreasing GANAB in Recent-Onset Schizophrenia. Viruses, 15.","DOI":"10.3390\/v15061298"},{"key":"ref_57","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_58","doi-asserted-by":"crossref","unstructured":"Yao, W., Zhou, P., Yan, Q., Wu, X., Xia, Y., Li, W., Li, X., and Zhu, F. (2023). ERVWE1 Reduces Hippocampal Neuron Density and Impairs Dendritic Spine Morphology through Inhibiting Wnt\/JNK Non-Canonical Pathway via miR-141-3p in Schizophrenia. Viruses, 15.","DOI":"10.3390\/v15010168"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1186\/s13578-023-01167-4","article-title":"Captive ERVWE1 triggers impairment of 5-HT neuronal plasticity in the first-episode schizophrenia by post-transcriptional activation of HTR1B in ALKBH5-m6A dependent epigenetic mechanisms","volume":"13","author":"Wu","year":"2023","journal-title":"Cell Biosci."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Li, X., Wu, X., Li, W., Yan, Q., Zhou, P., Xia, Y., Yao, W., and Zhu, F. (2023). HERV-W ENV Induces Innate Immune Activation and Neuronal Apoptosis via linc01930\/cGAS Axis in Recent-Onset Schizophrenia. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24033000"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.virs.2023.09.001","article-title":"Ancient dormant virus remnant ERVW-1 drives ferroptosis via degradation of GPX4 and SLC3A2 in schizophrenia","volume":"39","author":"Zhang","year":"2024","journal-title":"Virol. Sin."},{"key":"ref_62","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_63","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_64","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-\u03b1 and IL-10 by inhibiting MyD88s in glial cells","volume":"166","author":"Wang","year":"2021","journal-title":"Arch. Virol."},{"key":"ref_65","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_66","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41398-019-0492-8","article-title":"Postmortem transcriptional profiling reveals widespread increase in inflammation in schizophrenia: A comparison of prefrontal cortex, striatum, and hippocampus among matched tetrads of controls with subjects diagnosed with schizophrenia, bipolar or major depressive disorder","volume":"9","author":"Lanz","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kumar, A., Pareek, V., Singh, H.N., Faiq, M.A., Narayan, R.K., Raza, K., and Kumar, P. (2019). Altered Expression of a Unique Set of Genes Reveals Complex Etiology of Schizophrenia. Front Psychiatry, 10.","DOI":"10.3389\/fpsyt.2019.00906"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.schres.2022.08.027","article-title":"Mitochondrial dysfunction in psychiatric disorders","volume":"273","author":"Ni","year":"2024","journal-title":"Schizophr. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"eadh0558","DOI":"10.1126\/sciadv.adh0558","article-title":"Cross-species analysis identifies mitochondrial dysregulation as a functional consequence of the schizophrenia-associated 3q29 deletion","volume":"9","author":"Purcell","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2319412","DOI":"10.1155\/2021\/2319412","article-title":"Baicalein Mediates Mitochondrial Autophagy via miR-30b and the NIX\/BNIP3 Signaling Pathway in Parkinson\u2019s Disease","volume":"2021","author":"Chen","year":"2021","journal-title":"Biochem. Res. Int."},{"key":"ref_71","first-page":"152","article-title":"Iron Dysregulation in Neurodegeneration with Brain Iron Accumulation (NBIA): Links between Mutations Occurring in BPAN, PKAN, MPAN and PLAN Types and Iron Metabolism","volume":"63","author":"Szota","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"101003","DOI":"10.1016\/j.xgen.2025.101003","article-title":"Network-based drug repurposing for psychiatric disorders using single-cell genomics","volume":"5","author":"Gupta","year":"2025","journal-title":"Cell Genom."},{"key":"ref_73","first-page":"e12251","article-title":"Plasma microRNA vary in association with the progression of Alzheimer\u2019s disease","volume":"14","author":"Tsui","year":"2022","journal-title":"Alzheimer\u2019s Dement."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Fazeli, S., Motovali-Bashi, M., Peymani, M., Hashemi, M.S., Etemadifar, M., Nasr-Esfahani, M.H., and Ghaedi, K. (2020). A compound downregulation of SRRM2 and miR-27a-3p with upregulation of miR-27b-3p in PBMCs of Parkinson\u2019s patients is associated with the early stage onset of disease. PLoS ONE, 15, Erratum in PLoS ONE 2020, 15, e0244776. https:\/\/doi.org\/10.1371\/journal.pone.0244776.","DOI":"10.1371\/journal.pone.0244776"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Cronan, J.E. (2020). Progress in the Enzymology of the Mitochondrial Diseases of Lipoic Acid Requiring Enzymes. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.00510"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"107404","DOI":"10.5498\/wjp.v15.i8.107404","article-title":"Cell-free DNA in extracellular vesicles: A candidate biomarker of schizophrenia","volume":"15","author":"Bai","year":"2025","journal-title":"World J. Psychiatry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/gtc.12278","article-title":"Baton pass hypothesis: Successive incorporation of unconserved endogenous retroviral genes for placentation during mammalian evolution","volume":"20","author":"Imakawa","year":"2015","journal-title":"Genes Cells"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1126\/science.aaw7733","article-title":"IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise","volume":"365","author":"Buchrieser","year":"2019","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Tagliaferri, S., Cepparulo, P., Vinciguerra, A., Campanile, M., Esposito, G., Maruotti, G.M., Zullo, F., Annunziato, L., and Pignataro, G. (2021). miR-16-5p, miR-103-3p, and miR-27b-3p as Early Peripheral Biomarkers of Fetal Growth Restriction. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.611112"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"101854","DOI":"10.1016\/j.redox.2021.101854","article-title":"Melatonin protects against environmental stress-induced fetal growth restriction via suppressing ROS-mediated GCN2\/ATF4\/BNIP3-dependent mitophagy in placental trophoblasts","volume":"40","author":"Zhu","year":"2021","journal-title":"Redox Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"861","DOI":"10.14348\/molcells.2021.5016","article-title":"Human Endogenous Retroviruses as Gene Expression Regulators: Insights from Animal Models into Human Diseases","volume":"44","author":"Durnaoglu","year":"2021","journal-title":"Mol. Cells"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Bao, C., Gao, Q., Xiang, H., Shen, Y., Chen, Q., Gao, Q., Cao, Y., Zhang, M., He, W., and Mao, L. (2024). Human endogenous retroviruses and exogenous viral infections. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1439292"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1007\/s11262-017-1479-2","article-title":"HBV X Protein induces overexpression of HERV-W env through NF-\u03baB in HepG2 cells","volume":"53","author":"Liu","year":"2017","journal-title":"Virus Genes"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/2\/245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:21:19Z","timestamp":1771305679000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/2\/245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,14]]},"references-count":83,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["v18020245"],"URL":"https:\/\/doi.org\/10.3390\/v18020245","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,14]]}}}