{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:45:11Z","timestamp":1791337511807,"version":"4.3.1"},"reference-count":47,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"2025 Current Research Funds","doi-asserted-by":"publisher","award":["RRC-2025-23686388"],"award-info":[{"award-number":["RRC-2025-23686388"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Altered protein synthesis plays a key role in ageing and multiple neurodegenerative diseases. In Alzheimer\u2019s disease and other tauopathies, the intracellular accumulation of hyperphosphorylated Tau disrupts several cellular processes, including mRNA translation. Although Tau interacts with ribosomal proteins and modulates translational selectivity, its effects on global protein synthesis remain poorly understood. Studies report reduced translation in later disease stages but increased translation early in pathology. To clarify Tau\u2019s impact in human neurons, we used SH-SY5Y cells overexpressing the P301L mutant form of Tau and quantified global protein synthesis using the SUnSET (Surface Sensing of Translation) puromycin-incorporation assay. We found that Tau-P301L expression greatly increased global translation by upregulating mTOR\/S6 pathway. These effects were abolished by rapamycin treatment, indicating that Tau-driven translational upregulation is mTOR-dependent. Given that impaired translational control can disrupt synaptic plasticity and memory, Tau-induced alterations in protein synthesis may contribute to tauopathy progression and identify mTOR signalling as a potential therapeutic target.<\/jats:p>","DOI":"10.3390\/ijms27010455","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T11:11:46Z","timestamp":1767352306000},"page":"455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mutant Tau (P301L) Enhances Global Protein Translation in Differentiated SH-SY5Y Cells by Upregulating mTOR Signalling"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0823-1455","authenticated-orcid":false,"given":"Giovanni Luca","family":"Cipriano","sequence":"first","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Floramo","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Argento","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7304-7430","authenticated-orcid":false,"given":"Salvatore","family":"Oddo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences (ChiBioFarAm), University of Messina, Viale F. Stagno d\u2019Alcontres 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8771-0317","authenticated-orcid":false,"given":"Osvaldo","family":"Artimagnella","sequence":"additional","affiliation":[{"name":"IRCCS Centro Neurolesi \u201cBonino-Pulejo\u201d, Via Provinciale Palermo, Contrada Casazza, 98124 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1146\/annurev-pathmechdis-051222-120750","article-title":"Neurodegenerative Disease Tauopathies","volume":"19","author":"Creekmore","year":"2024","journal-title":"Annu. Rev. Pathol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101644","DOI":"10.1016\/j.pneurobio.2019.101644","article-title":"Four-repeat tauopathies","volume":"180","author":"Rosler","year":"2019","journal-title":"Prog. 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