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http://ntour.ntou.edu.tw:8080/ir/handle/987654321/43540
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| Title: | Presenilin-1 Regulates the Expression of p62 to Govern p62-dependent Tau Degradation |
| Authors: | Ying-Tsen Tung;Bo-Jeng Wang;Wen-Ming Hsu;Ming-Kuan Hu;Guor Mour Her;Wei-Pang Huang;Yung-Feng Liao |
| Contributors: | 國立臺灣海洋大學:生命科學系 |
| Keywords: | Presenilin;p62;Tau;Alzheimer’s disease Autophagy;γ-Secretase |
| Date: | 2013-06-23
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| Issue Date: | 2017-09-15T02:11:55Z
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| Publisher: | Molecular Neurobiology |
| Abstract: | Abstract:Mutations in presenilin-1 (PS1) are tightly associated with early-onset familial Alzheimer’s disease (FAD), which is characterized by extracellular amyloid plaques and the accumulation of intracellular Tau. In addition to being the catalytic subunit of γ-secretase, PS1 has been shown to regulate diverse cellular functions independent of its proteolytic activity. We found that cells deficient in PS1 exhibit reduced levels of p62 protein, a cargo-receptor shuttling Tau for degradation. The downregulation of PS1 led to a significant decrease in both the protein and mRNA transcript of p62, concomitant with attenuated p62 promoter activity. This PS1-dependent regulation of p62 expression was mediated through an Akt/AP-1 pathway independent of the proteolytic activity of PS1/γ-secretase. This p62-mediated Tau degradation was significantly impaired in PS1-deficient cells, which can be rescued by ectopic expression of either p62 or wild-type PS1 but not mutant PS1 containing FAD-linked mutations. Our study suggests a novel function for PS1 in modulating p62 expression to control the proteostasis of Tau. |
| Relation: | 49(1), pp.10-27 |
| URI: | http://ntour.ntou.edu.tw:8080/ir/handle/987654321/43540 |
| Appears in Collections: | [生命科學系] 期刊論文
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