{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T14:14:18Z","timestamp":1772547258752,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"publisher","award":["2023YFC2306000"],"award-info":[{"award-number":["2023YFC2306000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"SKLID Development Grants","award":["2021SKLID504"],"award-info":[{"award-number":["2021SKLID504"]}]},{"name":"SKLID Development Grants","award":["2019SKLID401"],"award-info":[{"award-number":["2019SKLID401"]}]},{"name":"SKLID Development Grants","award":["2019SKLID603"],"award-info":[{"award-number":["2019SKLID603"]}]},{"name":"SKLID Development Grants","award":["2021SKLID503"],"award-info":[{"award-number":["2021SKLID503"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prion diseases are fatal neurodegenerative disorders characterized by profound neuronal damage. Despite evidence supporting a neuroprotective role for \u03b2-synuclein (\u03b2-syn) in neurodegeneration, its potential functions and mechanisms in prion disease have not been elucidated. To investigate the role of \u03b2-syn, we systematically analyzed its alterations in the central nervous system of several prion-infected rodent models and cell models. A series of biochemical, cellular, and immunofluorescence assays were conducted to explore the relationship between \u03b2-syn and protein kinase B (Akt) signaling and between \u03b2-syn and prion protein (PrP), and its neuroprotective role in prion disease. Student\u2019s t-test was used for statistics. At the terminal stage of prion disease, \u03b2-syn and Akt exhibited a parallel and remarkable decrease in rodent brains, contrasting with the slight but significant increase observed at early to middle stages. Dual-stained immunofluorescence assays confirmed that \u03b2-syn is localized within NeuN-positive neurons. Further structural and functional analyses revealed a high-affinity molecular interaction between \u03b2-syn and Akt, with the N-terminal region of \u03b2-syn being essential for binding to Akt1. In a cell model of PrP aggregation, \u03b2-syn overexpression suppressed cytochrome c-induced apoptosis, which was demonstrated by decreased levels of cleaved caspase-3. Notably, this anti-apoptotic effect was partially abolished upon Akt knockdown, indicating a dependence on Akt signaling. Moreover, colocalization of \u03b2-syn and PrP was observed in rodent brains. Consistently, in cellular models of prion infection and PrP aggregation, \u03b2-syn overexpression not only reduced PrP levels but also ameliorated its aberrant histological distribution. Our findings demonstrate that the anti-apoptotic activity of \u03b2-syn, mediated via Akt signaling, is severely lost during prion infection, thereby suggesting a mechanism of intrinsic neuronal vulnerability and revealing a novel therapeutic strategy.<\/jats:p>","DOI":"10.3390\/ijms27052344","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T09:45:12Z","timestamp":1772531112000},"page":"2344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Anti-Apoptotic Activity of \u03b2-Synuclein Mediated via Akt Signaling Is Severely Lost During Prion Infection"],"prefix":"10.3390","volume":"27","author":[{"given":"Bing","family":"Xu","sequence":"first","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang","family":"Xiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6770-6073","authenticated-orcid":false,"given":"Rui","family":"Xu","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese 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Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juzheng","family":"Li","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinghao","family":"Zhai","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruhan","family":"A","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7022-0418","authenticated-orcid":false,"given":"Liping","family":"Gao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rundong","family":"Cao","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-9283","authenticated-orcid":false,"given":"Cao","family":"Chen","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Shi","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-8447","authenticated-orcid":false,"given":"Xiaoping","family":"Dong","sequence":"additional","affiliation":[{"name":"National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Disease, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Chinese Academy of Preventive Medicine, Beijing 102206, China"},{"name":"Shanghai Institute of Infectious Disease and Biosafety, Shanghai 200003, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13363","DOI":"10.1073\/pnas.95.23.13363","article-title":"Prions","volume":"95","author":"Prusiner","year":"1998","journal-title":"Proc. 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