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Hyperphosphorylation of tau, which leads to formation of neurofibrillary tangles in Alzheimer\u2019s disease, is increased by endoplasmic reticulum (ER) stress. Selenoprotein S (SelS) is part of an ER membrane complex that removes misfolded proteins from the ER as a\u00a0means to reduce ER stress. Selenate, as with other forms of selenium, will increase selenoprotein expression. We therefore proposed that increased SelS expression by selenate would contribute to the beneficial actions of selenate in Alzheimer\u2019s disease. SelS expression increased with ER stress and decreased under conditions of elevated glucose concentrations in the SH-SY5Y neuronal cell line. Reducing expression of SelS with siRNA promoted cell death in response to ER stress. Selenate increased SelS expression, which significantly correlated with decreased tau phosphorylation. Restricting SelS expression during ER stress conditions increased tau phosphorylation, and also promoted aggregation of phosphorylated tau in neurites and soma. In human postmortem brain, SelS expression coincided with neurofibrillary tangles, but not with amyloid-\u03b2 plaques. These results indicate that selenate can alter phosphorylation of tau by increasing expression of SelS in Alzheimer\u2019s disease and potentially other neurodegenerative disorders.<\/jats:p>","DOI":"10.3233\/jad-151208","type":"journal-article","created":{"date-parts":[[2016,10,11]],"date-time":"2016-10-11T12:07:43Z","timestamp":1476187663000},"page":"749-762","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":53,"title":["Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology"],"prefix":"10.1177","volume":"55","author":[{"given":"Rachel H.L.H.","family":"Rueli","sequence":"first","affiliation":[{"name":"University of Hawai\u2019i at Manoa","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Torres","sequence":"additional","affiliation":[{"name":"University of Hawai\u2019i at 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