論文 - 詳細
| RRC ID | 30210 |
|---|---|
| 著者 | Jo C, Gundemir S, Pritchard S, Jin YN, Rahman I, Johnson GV. |
| タイトル | Nrf2 reduces levels of phosphorylated tau protein by inducing autophagy adaptor protein NDP52. |
| ジャーナル | Nat Commun |
| Abstract |
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor in the defence against oxidative stress. Here we provide evidence that activation of the Nrf2 pathway reduces the levels of phosphorylated tau by induction of an autophagy adaptor protein NDP52 (also known as CALCOCO2) in neurons. The expression of NDP52, which we show has three antioxidant response elements (AREs) in its promoter region, is strongly induced by Nrf2, and its overexpression facilitates clearance of phosphorylated tau in the presence of an autophagy stimulator. In Nrf2-knockout mice, phosphorylated and sarkosyl-insoluble tau accumulates in the brains concurrent with decreased levels of NDP52. Moreover, NDP52 associates with phosphorylated tau from brain cortical samples of Alzheimer disease cases, and the amount of phosphorylated tau in sarkosyl-insoluble fractions is inversely proportional to that of NDP52. These results suggest that NDP52 plays a key role in autophagy-mediated degradation of phosphorylated tau in vivo. |
| 巻・号 | 5 |
| ページ | 3496 |
| 公開日 | 2014-3-25 |
| DOI | 10.1038/ncomms4496 |
| PII | ncomms4496 |
| PMID | 24667209 |
| PMC | PMC3990284 |
| MeSH | Aged Aged, 80 and over Alzheimer Disease / metabolism* Animals Autophagy* Brain / metabolism* Cerebral Cortex / metabolism Female HEK293 Cells Hippocampus / metabolism Humans Maf Transcription Factors / metabolism Male Mice Mice, Knockout NF-E2-Related Factor 2 / genetics* NF-E2-Related Factor 2 / metabolism Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Neurons / metabolism Nuclear Proteins / genetics* Nuclear Proteins / metabolism Oxidative Stress Phosphorylation RNA, Messenger / metabolism* Rats Receptors, Cytoplasmic and Nuclear / genetics* Receptors, Cytoplasmic and Nuclear / metabolism Reverse Transcriptase Polymerase Chain Reaction tau Proteins / metabolism* |
| IF | 12.121 |
| 引用数 | 154 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| リソース情報 | |
| 実験動物マウス | RBRC01390 |