Article ; Online: Selenoprotein S Reduces Endoplasmic Reticulum Stress-Induced Phosphorylation of Tau: Potential Role in Selenate Mitigation of Tau Pathology.
Journal of Alzheimer's disease : JAD
2016 Volume 55, Issue 2, Page(s) 749–762
Abstract: ... of neurofibrillary tangles in Alzheimer's disease, is increased by endoplasmic reticulum (ER) stress. Selenoprotein S (SelS ... tau phosphorylation. Restricting SelS expression during ER stress conditions increased tau ... stress. Selenate, as with other forms of selenium, will increase selenoprotein expression ...
| Abstract | Previous studies demonstrated that selenium in the form of sodium selenate reduces neurofibrillary tangle formation in Alzheimer's disease models. Hyperphosphorylation of tau, which leads to formation of neurofibrillary tangles in Alzheimer's 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 means 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's 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-β plaques. These results indicate that selenate can alter phosphorylation of tau by increasing expression of SelS in Alzheimer's disease and potentially other neurodegenerative disorders. |
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| MeSH term(s) | Aged ; Aged, 80 and over ; Analysis of Variance ; Brain/metabolism ; Cell Line, Tumor ; Endoplasmic Reticulum Stress/drug effects ; Endoplasmic Reticulum Stress/physiology ; Gene Expression Regulation/genetics ; Glucose/pharmacology ; Humans ; Leucine/genetics ; Membrane Proteins/genetics ; Membrane Proteins/pharmacology ; Mutation/genetics ; Neuroblastoma/pathology ; Phosphorylation/drug effects ; Proline/genetics ; RNA, Messenger/metabolism ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Selenoproteins/genetics ; Selenoproteins/pharmacology ; Transfection ; tau Proteins/metabolism | |||||
| Chemical Substances | Membrane Proteins ; RNA, Messenger ; RNA, Small Interfering ; SELENOS protein, human ; Selenoproteins ; tau Proteins ; Proline (9DLQ4CIU6V) ; Leucine (GMW67QNF9C) ; Glucose (IY9XDZ35W2) | |||||
| Language | English | |||||
| Publishing date | 2016-11-02 | |||||
| Publishing country | Netherlands | |||||
| Document type | Journal Article | |||||
| ZDB-ID | 1440127-7 | |||||
| ISSN | 1875-8908 ; 1387-2877 | |||||
| ISSN (online) | 1875-8908 | |||||
| ISSN | 1387-2877 | |||||
| DOI | 10.3233/JAD-151208 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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