{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T15:18:53Z","timestamp":1778167133418,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Hacettepe University Scientific Projects Coordination Unit","award":["THD-2021-19660"],"award-info":[{"award-number":["THD-2021-19660"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Epigenetic dysregulation is increasingly recognized as a key mechanism in the development and progression of Alzheimer's disease (AD). Herpes simplex virus type 1 (HSV-1) infection has been proposed as a potential biological trigger that may accelerate neurodegeneration through epigenetic modifications. Among HSV-1 structural proteins, glycoprotein B (HSV-gB) may influence host\u2013virus interactions affecting neuronal gene regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate the contribution of HSV-gB to AD-related epigenetic alterations and to determine whether HSV-gB exposure exacerbates epigenetic dysregulation in two in vitro neuronal AD models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human SH-SY5Y neuroblastoma cells were used to establish two AD models: a differentiation-based aging model induced by retinoic acid and brain-derived neurotrophic factor (RA\u2009+\u2009BDNF), and an amyloid aggregation model induced by amyloid-\u03b2 1\u201342 (A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      ). Cells were treated with HSV-gB (190.5 pg\/ml) alone or in combination with each model. Global DNA methylation, histone H3 and H4 acetylation, histone multiplex modifications, and HDAC3 and HDAC8 levels were analyzed using ELISA-based assays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HSV-gB exposure and RA\u2009+\u2009BDNF treatment induced global DNA hypomethylation and histone hypoacetylation, accompanied by significant increases in HDAC3 and HDAC8 levels. In contrast, the A\u03b2\n                      <jats:sub>1\u201342<\/jats:sub>\n                      model showed DNA hypermethylation and histone hyperacetylation, indicating distinct epigenetic profiles between differentiation-associated aging and amyloid-driven pathology.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HSV-gB contributes to AD-related epigenetic dysregulation and may amplify neurodegenerative mechanisms through HDAC-mediated chromatin remodeling. The findings highlight divergent epigenetic signatures in different AD models and support a potential role for viral factors in modulating AD-associated epigenetic pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261427784","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:41:03Z","timestamp":1773394863000},"page":"1886-1898","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Determination of the effects of\n                    <i>Herpes simplex<\/i>\n                    glycoprotein B on epigenetic alterations in in vitro models of Alzheimer's disease"],"prefix":"10.1177","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4050-8832","authenticated-orcid":false,"given":"Anil","family":"Yir\u00fcn","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Alt\u0131ndag\/Ankara, Turkey"},{"name":"Department of Pharmaceutical Toxicology, Cukurova University Faculty of Pharmacy, Sar\u0131\u00e7am\/Adana, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deniz Arca","family":"\u00c7ak\u0131r","sequence":"additional","affiliation":[{"name":"Department of Vaccine Technology, Hacettepe University Vaccine Institute, Alt\u0131ndag\/Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selinay Ba\u015fak","family":"Erdemli K\u00f6se","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Alt\u0131ndag\/Ankara, Turkey"},{"name":"Department of Chemistry, Burdur Mehmet Akif Ersoy University Faculty of Arts and Sciences, Merkez\/Burdur, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aylin Balc\u0131","family":"\u00d6zyurt","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Alt\u0131ndag\/Ankara, Turkey"},{"name":"Department of Pharmaceutical Toxicology, Bah\u00e7e\u015fehir University Faculty of Pharmacy, Be\u015fikta\u015f\/Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00f6ksun","family":"Demirel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Cukurova University Faculty of Pharmacy, Sar\u0131\u00e7am\/Adana, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinar","family":"Erkekoglu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Hacettepe University Faculty of Pharmacy, Alt\u0131ndag\/Ankara, Turkey"},{"name":"Department of Vaccine Technology, Hacettepe University Vaccine Institute, Alt\u0131ndag\/Ankara, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)09420-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.111"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2014.01.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00097"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100044115"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.09.077"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013989"},{"key":"e_1_3_3_9_2","article-title":"Herpes simplex virus dances with amyloid precursor protein while exiting the cell","volume":"6","author":"Cheng SB","year":"2011","unstructured":"Cheng SB, Ferland P, Webster P, et al. 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