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Additionally, the presence of herpes simplex virus type 1 (HSV-1) in the brains of AD patients has long been suggested as a contributing factor for AD. However, mechanisms by which HSV-1 accelerates AD pathogenesis remain poorly understood. Here we report that HSV-1 infection induces hyperphosphorylation of cofilin in the brains of 5\u00d7FAD mice. Cofilin is an actin depolymerizing factor, and its S3 phosphorylation inactivates cofilin\u2019s activity to depolymerize actin filaments. These findings facilitate the understanding of impacts of HSV-1 infection on the development of Alzheimer\u2019s disease and have implications in AD therapeutics.<\/jats:p>","DOI":"10.1101\/2025.08.10.669568","type":"posted-content","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T19:55:45Z","timestamp":1755028545000},"source":"Crossref","is-referenced-by-count":0,"title":["HSV-1 infection induces brain cofilin hyperphosphorylation in the 5\u00d7FAD Alzheimer\u2019s Disease mouse model"],"prefix":"10.64898","author":[{"given":"Laia","family":"Gharavi-naeini","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenfeng","family":"Shu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhang","family":"Alem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda D.","family":"Chilin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pinghui","family":"Feng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuntao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025081423151656000_2025.08.10.669568v1.1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: mechanisms, clinical trials and new drug development strategies","volume":"9","year":"2024","journal-title":"Signal Transduction and Targeted Therapy"},{"key":"2025081423151656000_2025.08.10.669568v1.2","doi-asserted-by":"crossref","first-page":"102699","DOI":"10.1016\/j.arr.2025.102699","article-title":"Hallmarks of aging and Alzheimer\u2019s Disease pathogenesis: Paving the route for new therapeutic targets","volume":"106","year":"2025","journal-title":"Ageing Research Reviews"},{"key":"2025081423151656000_2025.08.10.669568v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/35023579"},{"key":"2025081423151656000_2025.08.10.669568v1.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1994.tb00951.x"},{"key":"2025081423151656000_2025.08.10.669568v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.11.025"},{"key":"2025081423151656000_2025.08.10.669568v1.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.15.1.185"},{"key":"2025081423151656000_2025.08.10.669568v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/31735"},{"key":"2025081423151656000_2025.08.10.669568v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/31729"},{"key":"2025081423151656000_2025.08.10.669568v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2571(02)00031-6"},{"key":"2025081423151656000_2025.08.10.669568v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00638-9"},{"key":"2025081423151656000_2025.08.10.669568v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1201"},{"key":"2025081423151656000_2025.08.10.669568v1.12","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200809046"},{"key":"2025081423151656000_2025.08.10.669568v1.13","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507675102"},{"key":"2025081423151656000_2025.08.10.669568v1.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.23.7590"},{"key":"2025081423151656000_2025.08.10.669568v1.15","doi-asserted-by":"crossref","unstructured":"Y. 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