{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:51:36Z","timestamp":1782237096904,"version":"3.54.5"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS-2024-00397713"],"award-info":[{"award-number":["RS-2024-00397713"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","award":["RS-2025-23323581"],"award-info":[{"award-number":["RS-2025-23323581"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Tauopathies are neurodegenerative diseases characterized by the presence of hyperphosphorylated tau (p-tau) and neurofibrillary tangles. Autophagy is a critical self-degradation mechanism that preserves cellular homeostasis and function, including the clearance of misfolded proteins. Autophagy is impaired in tauopathies, resulting in excessive accumulation of p-tau. Omipalisib, a dual phosphatidylinositol 3-kinase\/mammalian target of rapamycin (PI3K\/mTOR) inhibitor, was explored in a phase I clinical trial involving solid tumors and lymphoma. In this study, we aimed to investigate the effects of omipalisib on tauopathy both\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Omipalisib increased the levels of protein LC3B and decreased that of p62 in human tau (P301L)-expressing SH-SY5Y stable (SH-Tau) cells by inhibiting mTOR activation in a time-dependent manner. In our study, we hypothesized that omipalisib, a PI3K\/mTOR inhibitor, could remove accumulated tau and inhibit memory decline by activating autophagy. Additionally, omipalisib reduced tau phosphorylation in SH-Tau cells without inducing cytotoxicity. Upon administration of 6-month-old PS19 mice with omipalisib (1 mg\/kg) for 2 months, the levels of both RIPA-soluble and RIPA-insoluble p-tau were decreased, and spatial memory dysfunction was alleviated in omipalisib-treated PS19 mice. Overall, these results show that omipalisib decreases the expression of p-tau by modulation mTOR-autophagy pathway, resulting in the amelioration of spatial memory deficits. This study highlighted the potential of omipalisib as a candidate treatment for tauopathies.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0352120","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:31:18Z","timestamp":1782235878000},"page":"e0352120","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Omipalisib reduces hyperphosphorylated tau protein by modulating mTOR-autophagy pathway"],"prefix":"10.1371","volume":"21","author":[{"given":"Haeun","family":"Hwang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namkwon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subyn","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojin","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongmin","family":"Son","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Ho","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Sung","family":"Gee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Soo","family":"Inn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2428-3530","authenticated-orcid":true,"given":"Jong Kil","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"issue":"24","key":"pone.0352120.ref001","doi-asserted-by":"crossref","first-page":"7501","DOI":"10.1073\/pnas.1504081112","article-title":"Tau stabilizes microtubules by binding at the interface between tubulin heterodimers","volume":"112","author":"H Kadavath","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0352120.ref002","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.bbadis.2004.06.017","article-title":"Tau phosphorylation: 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