{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T19:11:02Z","timestamp":1788462662691,"version":"build-2803163510"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018378","name":"Owens Family Foundation","doi-asserted-by":"publisher","award":["R01 AG067048"],"award-info":[{"award-number":["R01 AG067048"]}],"id":[{"id":"10.13039\/100018378","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018378","name":"Owens Family Foundation","doi-asserted-by":"publisher","award":["RF1 AG051085"],"award-info":[{"award-number":["RF1 AG051085"]}],"id":[{"id":"10.13039\/100018378","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007625","name":"CAF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cytoskeleton"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tau was discovered in the mid 1970's as a microtubule\u2010associated protein that stimulates tubulin polymerization, and subsequently was shown to be expressed primarily in neurons, where it is most concentrated in axons. Interest in tau rose by the late 1980's, when it was shown to be the principal subunit of the neurofibrillary tangles (NFTs) that accumulate in Alzheimer's disease (AD) brain, and achieved new heights by the late 1990's, when numerous tau mutations were found to be highly penetrant for AD\u2010related disorders that also are associated with NFTs and came to be known as non\u2010Alzheimer's tauopathies. The role of tau in neurodegeneration is far more complex than whatever effects on neurons may be caused by NFTs, however, and here we review our work on dysregulation of mTOR by tau in AD. mTOR is a protein kinase and master regulator of myriad aspects of cellular behavior. We have defined a complex signaling network whereby aberrant tau phosphorylation provoked by amyloid\u2010\u03b2 oligomers (A\u03b2Os), the building blocks of the amyloid plaques that form in AD brain, cause post\u2010mitotic neurons to re\u2010enter the cell cycle, but to die eventually instead of dividing, which may account for most neuron death in AD. Remarkably, we found that this same neuronal signaling network also poisons a fundamental cell biological process that we discovered, nutrient\u2010induced mitochondrial activation, or NiMA. Tau\u2010dependent cell cycle re\u2010entry and NiMA inhibition occur in cultured neurons within a few hours of exposure to A\u03b2Os, and thus may represent seminal processes in AD pathogenesis.<\/jats:p>","DOI":"10.1002\/cm.21782","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T12:27:13Z","timestamp":1693225633000},"page":"30-34","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Dysregulation of <scp>mTOR<\/scp> by tau in Alzheimer's disease"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4781-7627","authenticated-orcid":false,"given":"George S.","family":"Bloom","sequence":"first","affiliation":[{"name":"Department of Biology University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Cell Biology University of Virginia  Charlottesville Virginia USA"},{"name":"Department of Neuroscience University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2977-1709","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Norambuena","sequence":"additional","affiliation":[{"name":"Department of Biology University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,28]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2012.287"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5562"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.110957"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090955"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(93)90279-Z"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0777-14.2014"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-22-09733.2002"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00867-07"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200403069"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1886-z"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0205-1"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-5869"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1054\/mehy.1997.0680"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105737"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2018100241"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.015"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12892"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.1125880"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0009979"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0036-2"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02866"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2441-08.2008"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-07-02557.2003"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3025"}],"container-title":["Cytoskeleton"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cm.21782","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T05:32:59Z","timestamp":1705987979000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cm.21782"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,28]]},"references-count":24,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1002\/cm.21782"],"URL":"https:\/\/doi.org\/10.1002\/cm.21782","archive":["Portico"],"relation":{},"ISSN":["1949-3584","1949-3592"],"issn-type":[{"value":"1949-3584","type":"print"},{"value":"1949-3592","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,28]]},"assertion":[{"value":"2023-08-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}